|Publication number||US8718789 B2|
|Application number||US 12/762,891|
|Publication date||6 May 2014|
|Filing date||19 Apr 2010|
|Priority date||27 Sep 2000|
|Also published as||US7499742, US7813812, US8060206, US8712531, US8880190, US9044609, US9427583, US20040010303, US20070021790, US20070021792, US20070021794, US20070021796, US20070021797, US20070021798, US20070021799, US20070038255, US20070038262, US20070106340, US20080097540, US20080167694, US20090228065, US20100191303, US20100222831, US20110172734, US20120130447, US20120232613, US20130090700, US20150238763, US20170001013|
|Publication number||12762891, 762891, US 8718789 B2, US 8718789B2, US-B2-8718789, US8718789 B2, US8718789B2|
|Inventors||Stephen L. Bolea, Robert S. Kieval, Bruce J. Persson, David J. Serdar, Peter T. Keith, Eric D. Irwin, Martin A. Rossing|
|Original Assignee||Cvrx, Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (388), Non-Patent Citations (76), Referenced by (4), Classifications (17), Legal Events (2)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This application is a continuation of U.S. application Ser. No. 11/535,666, filed Sep. 27, 2006, which is a continuation of U.S. application Ser. No. 10/402,911, filed on Mar. 27, 2003, now issued as U.S. Pat. No. 7,499,742 which is (1) a continuation-in-part of U.S. application Ser. No. 09/963,777, filed on Sep. 26, 2001, now issued as U.S. Pat. No. 7,158,832, which is a continuation-in-part of U.S. patent application Ser. No. 09/671,850, filed on Sep. 27, 2000, now issued as U.S. Pat. No. 6,522,926; and (2) claims the benefit of U.S. Provisional Application No. 60/368,222, filed on Mar. 27, 2002. The full disclosures of each of these applications are incorporated herein by reference. Parent application Ser. No. 10/402,911 has incorporated by reference the disclosures of the following applications: U.S. application Ser. No. 09/964,079, filed on Sep. 26, 2001, now issued as U.S. Pat. No. 6,985,774, and U.S. application Ser. No. 09/963,991, filed on Sep. 26, 2001, now issued as U.S. Pat. No. 6,850,801, the disclosures of which are also effectively incorporated by reference herein.
The present invention generally relates to medical devices and methods of use for the treatment and/or management of cardiovascular and renal disorders. Specifically, the present invention relates to devices and methods for controlling the baroreflex system for the treatment and/or management of cardiovascular and renal disorders and their underlying causes and conditions.
Cardiovascular disease is a major contributor to patient illness and mortality. It also is a primary driver of health care expenditure, costing more than $326 billion each year in the United States. Hypertension, or high blood pressure, is a major cardiovascular disorder that is estimated to affect over 50 million people in the United Sates alone. Of those with hypertension, it is reported that fewer than 30% have their blood pressure under control. Hypertension is a leading cause of heart failure and stroke. It is the primary cause of death in over 42,000 patients per year and is listed as a primary or contributing cause of death in over 200,000 patients per year in the U.S. Accordingly, hypertension is a serious health problem demanding significant research and development for the treatment thereof.
Hypertension occurs when the body's smaller blood vessels (arterioles) constrict, causing an increase in blood pressure. Because the blood vessels constrict, the heart must work harder to maintain blood flow at the higher pressures. Although the body may tolerate short periods of increased blood pressure, sustained hypertension may eventually result in damage to multiple body organs, including the kidneys, brain, eyes and other tissues, causing a variety of maladies associated therewith. The elevated blood pressure may also damage the lining of the blood vessels, accelerating the process of atherosclerosis and increasing the likelihood that a blood clot may develop. This could lead to a heart attack and/or stroke. Sustained high blood pressure may eventually result in an enlarged and damaged heart (hypertrophy), which may lead to heart failure.
Heart failure is the final common expression of a variety of cardiovascular disorders, including ischemic heart disease. It is characterized by an inability of the heart to pump enough blood to meet the body's needs and results in fatigue, reduced exercise capacity and poor survival. It is estimated that approximately 5,000,000 people in the United States suffer from heart failure, directly leading to 39,000 deaths per year and contributing to another 225,000 deaths per year. It is also estimated that greater than 400,000 new cases of heart failure are diagnosed each year. Heart failure accounts for over 900,000 hospital admissions annually, and is the most common discharge diagnosis in patients over the age of 65 years. It has been reported that the cost of treating heart failure in the United States exceeds $20 billion annually. Accordingly, heart failure is also a serious health problem demanding significant research and development for the treatment and/or management thereof.
Heart failure results in the activation of a number of body systems to compensate for the heart's inability to pump sufficient blood. Many of these responses are mediated by an increase in the level of activation of the sympathetic nervous system, as well as by activation of multiple other neurohormonal responses. Generally speaking, this sympathetic nervous system activation signals the heart to increase heart rate and force of contraction to increase the cardiac output; it signals the kidneys to expand the blood volume by retaining sodium and water; and it signals the arterioles to constrict to elevate the blood pressure. The cardiac, renal and vascular responses increase the workload of the heart, further accelerating myocardial damage and exacerbating the heart failure state. Accordingly, it is desirable to reduce the level of sympathetic nervous system activation in order to stop or at least minimize this vicious cycle and thereby treat or manage the heart failure.
A number of drug treatments have been proposed for the management of hypertension, heart failure and other cardiovascular disorders. These include vasodilators to reduce the blood pressure and ease the workload of the heart, diuretics to reduce fluid overload, inhibitors and blocking agents of the body's neurohormonal responses, and other medicaments.
Various surgical procedures have also been proposed for these maladies. For example, heart transplantation has been proposed for patients who suffer from severe, refractory heart failure. Alternatively, an implantable medical device such as a ventricular assist device (VAD) may be implanted in the chest to increase the pumping action of the heart. Alternatively, an intra-aortic balloon pump (IABP) may be used for maintaining heart function for short periods of time, but typically no longer than one month. Other surgical procedures are available as well.
It has been known for decades that the wall of the carotid sinus, a structure at the bifurcation of the common carotid arteries, contains stretch receptors (baroreceptors) that are sensitive to the blood pressure. These receptors send signals via the carotid sinus nerve to the brain, which in turn regulates the cardiovascular system to maintain normal blood pressure (the baroreflex), in part through activation of the sympathetic nervous system. Electrical stimulation of the carotid sinus nerve (baropacing) has previously been proposed to reduce blood pressure and the workload of the heart in the treatment of high blood pressure and angina. For example, U.S. Pat. No. 6,073,048 to Kieval et al. discloses a baroreflex modulation system and method for stimulating the baroreflex arc based on various cardiovascular and pulmonary parameters.
Although each of these alternative approaches is beneficial in some ways, each of the therapies has its own disadvantages. For example, drug therapy is often incompletely effective. Some patients may be unresponsive (refractory) to medical therapy. Drugs often have unwanted side effects and may need to be given in complex regimens. These and other factors contribute to poor patient compliance with medical therapy. Drug therapy may also be expensive, adding to the health care costs associated with these disorders. Likewise, surgical approaches are very costly, may be associated with significant patient morbidity and mortality and may not alter the natural history of the disease. Baropacing also has not gained acceptance. Several problems with electrical carotid sinus nerve stimulation have been reported in the medical literature. These include the invasiveness of the surgical procedure to implant the nerve electrodes, and postoperative pain in the jaw, throat, face and head during stimulation. In addition, it has been noted that high voltages sometimes required for nerve stimulation may damage the carotid sinus nerves. Accordingly, there continues to be a substantial and long felt need for new devices and methods for treating and/or managing high blood pressure, heart failure and their associated cardiovascular and nervous system disorders.
U.S. Pat. No. 6,522,926, signed to the Assignee of the present application, describes a number of systems and methods intended to activate baroreceptors in the carotid sinus and elsewhere in order to induce the baroreflex. Numerous specific approaches are described, including the use of coil electrodes placed over the exterior of the carotid sinus near the carotid bifurcation. While such electrode designs offer substantial promise, there is room for improvement in a number of specific design areas. For example, it would be desirable to provide designs which permit electrode structures to be closely and conformably secured over the exterior of a carotid sinus or other blood vessels so that efficient activation of the underlying baroreceptors can be achieved. It would be further desirable to provide specific electrode structures which can be variably positioned at different locations over the carotid sinus wall or elsewhere. At least some of these objectives will be met by these inventions described hereinbelow.
To address hypertension, heart failure and their associated cardiovascular and nervous system disorders, the present invention provides a number of devices, systems and methods by which the blood pressure, nervous system activity, and neurohormonal activity may be selectively and controllably regulated by activating baroreceptors. By selectively and controllably activating baroreceptors, the present invention reduces excessive blood pressure, sympathetic nervous system activation and neurohormonal activation, thereby minimizing their deleterious effects on the heart, vasculature and other organs and tissues.
The present invention provides systems and methods for treating a patient by inducing a baroreceptor signal to effect a change in the baroreflex system (e.g., reduced heart rate, reduced blood pressure, etc.). The baroreceptor signal is activated or otherwise modified by selectively activating baroreceptors. To accomplish this, the system and method of the present invention utilize a baroreceptor activation device positioned near a baroreceptor in the carotid sinus, aortic arch, heart, common carotid arteries, subclavian arteries, and/or brachiocephalic artery. Preferably, the baroreceptor activation device is located in the right and/or left carotid sinus (near the bifurcation of the common carotid artery) and/or the aortic arch. By way of example, not limitation, the present invention is described with reference to the carotid sinus location.
Generally speaking, the baroreceptor activation device may be activated, deactivated or otherwise modulated to activate one or more baroreceptors and induce a baroreceptor signal or a change in the baroreceptor signal to thereby effect a change in the baroreflex system. The baroreceptor activation device may be activated, deactivated, or otherwise modulated continuously, periodically, or episodically. The baroreceptor activation device may comprise a wide variety of devices which utilize electrodes to directly or indirectly activate the baroreceptor. The baroreceptor may be activated directly, or activated indirectly via the adjacent vascular tissue. The baroreceptor activation device will be positioned outside the vascular wall. To maximize therapeutic efficacy, mapping methods may be employed to precisely locate or position the baroreceptor activation device.
The present invention is directed particularly at electrical means and methods to activate baroreceptors, and various electrode designs are provided. The electrode designs may be particularly suitable for connection to the carotid arteries at or near the carotid sinus, and may be designed to minimize extraneous tissue stimulation. While being particularly suitable for use on the carotid arteries at or near the carotid sinus, the electrode structures and assemblies of the present invention will also find use for external placement and securement of electrodes about other arteries, and in some cases veins, having baroreceptor and other electrically activated receptors therein.
In a first aspect of the present invention, a baroreceptor activation device or other electrode useful for a carotid sinus or other blood vessel comprises a base having one or more electrodes connected to the base. The base has a length sufficient to extend around at least a substantial portion of the circumference of a blood vessel, usually an artery, more usually a carotid artery at or near the carotid sinus. By “substantial portion,” it is meant that the base will extend over at least 25% of the vessel circumference, usually at least 50%, more usually at least 66%, and often at least 75% or over the entire circumference. Usually, the base is sufficiently elastic to conform to said circumference or portion thereof when placed therearound. The electrode connected to the base is oriented at least partly in the circumferential direction and is sufficiently stretchable to both conform to the shape of the carotid sinus when the base is conformed thereover and accommodate changes in the shape and size of the sinus as they vary over time with heart pulse and other factors, including body movement which causes the blood vessel circumference to change.
Usually, at least two electrodes will be positioned circumferentially and adjacent to each other on the base. The electrode(s) may extend over the entire length of the base, but in some cases will extend over less than 75% of the circumferential length of the base, often being less than 50% of the circumferential length, and sometimes less than 25% of the circumferential length. Thus, the electrode structures may cover from a small portion up to the entire circumferential length of the carotid artery or other blood vessel. Usually, the circumferential length of the elongate electrodes will cover at least 10% of the circumference of the blood vessel, typically being at least 25%, often at least 50%, 75%, or the entire length. The base will usually have first and second ends, wherein the ends are adapted to be joined, and will have sufficient structural integrity to grasp the carotid sinus.
In a further aspect of the present invention, an extravascular electrode assembly comprises an elastic base and a stretchable electrode. The elastic base is adapted to be conformably attached over the outside of a target blood vessel, such as a carotid artery at or near the carotid sinus, and the stretchable electrode is secured over the elastic base and capable of expanding and contracting together with the base. In this way, the electrode assembly is conformable to the exterior of the carotid sinus or other blood vessel. Preferably, the elastic base is planar, typically comprising an elastomeric sheet. While the sheet may be reinforced, the reinforcement will be arranged so that the sheet remains elastic and stretchable, at least in the circumferential direction, so that the base and electrode assembly may be placed and conformed over the exterior of the blood vessel. Suitable elastomeric sheets may be composed of silicone, latex, and the like.
To assist in mounting the extravascular electrode over the carotid sinus or other blood vessel, the assembly will usually include two or more attachment tabs extending from the elastomeric sheet at locations which allow the tabs to overlap the elastic base and/or be directly attached to the blood vessel wall when the base is wrapped around or otherwise secured over a blood vessel. In this way, the tabs may be fastened to secure the backing over the blood vessel.
Preferred stretchable electrodes comprise elongated coils, where the coils may stretch and shorten in a spring-like manner. In particularly preferred embodiments, the elongated coils will be flattened over at least a portion of their lengths, where the flattened portion is oriented in parallel to the elastic base. The flattened coil provides improved electrical contact when placed against the exterior of the carotid sinus or other blood vessel.
In a further aspect of the present invention, an extravascular electrode assembly comprises a base and an electrode structure. The base is adapted to be attached over the outside of a carotid artery or other blood vessel and has an electrode-carrying surface formed over at least a portion thereof. A plurality of attachment tabs extend away from the electrode-carrying surface, where the tabs are arranged to permit selective ones thereof to be wrapped around a blood vessel while others of the tabs may be selectively removed. The electrode structure on or over the electrode-carrying surface.
In preferred embodiments, the base includes at least one tab which extends longitudinally from the electrode-carrying surface and at least two tabs which extend away from the surface at opposite, transverse angles. In an even more preferred embodiment, the electrode-carrying surface is rectangular, and at least two longitudinally extending tabs extend from adjacent corners of the rectangular surface. The two transversely angled tabs extend at a transverse angle away from the same two corners.
As with prior embodiments, the electrode structure preferably includes one or more stretchable electrodes secured to the electrode-carrying surface. The stretchable electrodes are preferably elongated coils, more preferably being “flattened coils” to enhance electrical contact with the blood vessel to be treated. The base is preferably an elastic base, more preferably being formed from an elastomeric sheet. The phrase “flattened coil,” as used herein, refers to an elongate electrode structure including a plurality of successive turns where the cross-sectional profile is non-circular and which includes at least one generally flat or minimally curved face. Such coils may be formed by physically deforming (flattening) a circular coil, e.g., as shown in
In a still further aspect of the present invention, a method for wrapping an electrode assembly over a blood vessel comprises providing an electrode assembly having an elastic base and one or more stretchable electrodes. The base is conformed over an exterior of the blood vessel, such as a carotid artery, and at least a portion of an electrode is stretched along with the base. Ends of the elastic base are secured together to hold the electrode assembly in place, typically with both the elastic backing and stretchable electrode remaining under at least slight tension to promote conformance to the vessel exterior. The electrode assembly will be located over a target site in the blood vessel, typically a target site having an electrically activated receptor. Advantageously, the electrode structures of the present invention when wrapped under tension will flex and stretch with expansions and contractions of the blood vessel. A presently preferred target site is a baroreceptor, particularly baroreceptors in or near the carotid sinus.
In a still further aspect of the present invention, a method for wrapping an electrode assembly over a blood vessel comprises providing an electrode assembly including a base having an electrode-carrying surface and an electrode structure on the electrode-carrying surface. The base is wrapped over a blood vessel, and some but not all of a plurality of attachment tags on the base are secured over the blood vessel. Usually, the tabs which are not used to secure an electrode assembly will be removed, typically by cutting. Preferred target sites are electrically activated receptors, usually baroreceptors, more usually baroreceptors on the carotid sinus. The use of such electrode assemblies having multiple attachment tabs is particularly beneficial when securing the electrode assembly on a carotid artery near the carotid sinus. By using particular tabs, as described in more detail below, the active electrode area can be positioned at any of a variety of locations on the common, internal, and/or external carotid arteries.
In another aspect, the present invention comprises pressure measuring assemblies including an elastic base adapted to be mounted on the outer wall of a blood vessel under circumferential tension. A strain measurement sensor is positioned on the base to measure strain resulting from circumferential expansion of the vessel due to a blood pressure increase. Usually, the base will wrap about the entire circumference of the vessel, although only a portion of the base need be elastic. Alternatively, a smaller base may be stapled, glued, clipped or otherwise secured over a “patch” of the vessel wall to detect strain variations over the underlying surface. Exemplary sensors include strain gauges and micro machined sensors (MEMS).
In yet another aspect, electrode assemblies according to the present invention comprise a base and at least three parallel elongate electrode structures secured over a surface of the base. The base is attachable to an outside surface of a blood vessel, such as a carotid artery, particularly a carotid artery near the carotid sinus, and has a length sufficient to extend around at least a substantial portion of the circumference of the blood vessel, typically extending around at least 25% of the circumference, usually extending around at least 50% of the circumference, preferably extending at least 66% of the circumference, and often extending around at least 75% of or the entire circumference of the blood vessel. As with prior embodiments, the base will preferably be elastic and composed of any of the materials set forth previously.
The at least three parallel elongate electrode structures will preferably be aligned in the circumferential direction of the base, i.e., the axis or direction of the base which will be aligned circumferentially over the blood vessel when the base is mounted on the blood vessel. The electrode structures will preferably be stretchable, typically being elongate coils, often being flattened elongate coils, as also described previously.
At least an outer pair of the electrode structures will be electrically isolated from an inner electrode structure, and the outer electrode structures will preferably be arranged in a U-pattern in order to surround the inner electrode structure. In this way, the outer pair of electrodes can be connected using a single conductor taken from the base, and the outer electrode structures and inner electrode structure may be connected to separate poles on a power supply in order to operate in the “pseudo” tripolar mode described hereinbelow.
To address low blood pressure and other conditions requiring blood pressure augmentation, the present invention provides electrode designs and methods utilizing such electrodes by which the blood pressure may be selectively and controllably regulated by inhibiting or dampening baroreceptor signals. By selectively and controllably inhibiting or dampening baroreceptor signals, the present invention reduces conditions associated with low blood pressure.
The following detailed description should be read with reference to the drawings in which similar elements in different drawings are numbered the same. The drawings, which are not necessarily to scale, depict illustrative embodiments and are not intended to limit the scope of the invention.
To better understand the present invention, it may be useful to explain some of the basic vascular anatomy associated with the cardiovascular system. Refer to
From the aortic arch 12, oxygenated blood flows into the carotid arteries 18/19 and the subclavian arteries 13/16. From the carotid arteries 18/19, oxygenated blood circulates through the head and cerebral vasculature and oxygen depleted blood returns to the heart 11 by way of the jugular veins, of which only the right internal jugular vein 21 is shown for sake of clarity. From the subclavian arteries 13/16, oxygenated blood circulates through the upper peripheral vasculature and oxygen depleted blood returns to the heart by way of the subclavian veins, of which only the right subclavian vein 23 is shown, also for sake of clarity. The heart 11 pumps the oxygen depleted blood through the pulmonary system where it is re-oxygenated. The re-oxygenated blood returns to the heart 11 which pumps the re-oxygenated blood into the aortic arch as described above, and the cycle repeats.
Within the arterial walls of the aortic arch 12, common carotid arteries 14/15 (near the right carotid sinus 20 and left carotid sinus), subclavian arteries 13/16 and brachiocephalic artery 22 there are baroreceptors 30. For example, as best seen in
Refer now to
Baroreceptor signals are used to activate a number of body systems which collectively may be referred to as the baroreflex system 50. Baroreceptors 30 are connected to the brain 52 via the nervous system 51. Thus, the brain 52 is able to detect changes in blood pressure, which is indicative of cardiac output. If cardiac output is insufficient to meet demand (i.e., the heart 11 is unable to pump sufficient blood), the baroreflex system 50 activates a number of body systems, including the heart 11, kidneys 53, vessels 54, and other organs/tissues. Such activation of the baroreflex system 50 generally corresponds to an increase in neurohormonal activity. Specifically, the baroreflex system 50 initiates a neurohormonal sequence that signals the heart 11 to increase heart rate and increase contraction force in order to increase cardiac output, signals the kidneys 53 to increase blood volume by retaining sodium and water, and signals the vessels 54 to constrict to elevate blood pressure. The cardiac, renal and vascular responses increase blood pressure and cardiac output 55, and thus increase the workload of the heart 11. In a patient with heart failure, this further accelerates myocardial damage and exacerbates the heart failure state.
To address the problems of hypertension, heart failure, other cardiovascular disorders and renal disorders, the present invention basically provides a number of devices, systems and methods by which the baroreflex system 50 is activated to reduce excessive blood pressure, autonomic nervous system activity and neurohormonal activation. In particular, the present invention provides a number of devices, systems and methods by which baroreceptors 30 may be activated, thereby indicating an increase in blood pressure and signaling the brain 52 to reduce the body's blood pressure and level of sympathetic nervous system and neurohormonal activation, and increase parasypathetic nervous system activation, thus having a beneficial effect on the cardiovascular system and other body systems.
With reference to
As mentioned previously, the baroreceptor activation device 70 may comprise a wide variety of devices which utilize electrical means to activate the baroreceptors 30. The baroreceptor activation device 70 of the present invention comprises an electrode structure which directly activates one or more baroreceptors 30 by changing the electrical potential across the baroreceptors 30. It is possible that changing the electrical potential across the tissue surrounding the baroreceptors 30 may cause the surrounding tissue to stretch or otherwise deform, thus mechanically activating the baroreceptors 30, in which case the stretchable and elastic electrode structures of the present invention may provide significant advantages.
All of the specific embodiments of the electrode structures of the present invention are suitable for implantation, and are preferably implanted using a minimally invasive surgical approach. The baroreceptor activation device 70 may be positioned anywhere baroreceptors 30 are present. Such potential implantation sites are numerous, such as the aortic arch 12, in the common carotid arteries 18/19 near the carotid sinus 20, in the subclavian arteries 13/16, in the brachiocephalic artery 22, or in other arterial or venous locations. The electrode structures of the present invention will be implanted such that they are positioned on or over a vascular structure immediately adjacent the baroreceptors 30. Preferably, the electrode structure of the baroreceptor activation device 70 is implanted near the right carotid sinus 20 and/or the left carotid sinus (near the bifurcation of the common carotid artery) and/or the aortic arch 12, where baroreceptors 30 have a significant impact on the baroreflex system 50. For purposes of illustration only, the present invention is described with reference to baroreceptor activation device 70 positioned near the carotid sinus 20.
The optional sensor 80 is operably coupled to the control system 60 by electric sensor cable or lead 82. The sensor 80 may comprise any suitable device that measures or monitors a parameter indicative of the need to modify the activity of the baroreflex system. For example, the sensor 80 may comprise a physiologic transducer or gauge that measures ECG, blood pressure (systolic, diastolic, average or pulse pressure), blood volumetric flow rate, blood flow velocity, blood pH, O.sub.2 or CO.sub.2 content, mixed venous oxygen saturation (SVO.sub.2), vasoactivity, nerve activity, tissue activity, body movement, activity levels, respiration, or composition. Examples of suitable transducers or gauges for the sensor 80 include ECG electrodes, a piezoelectric pressure transducer, an ultrasonic flow velocity transducer, an ultrasonic volumetric flow rate transducer, a thermodilution flow velocity transducer, a capacitive pressure transducer, a membrane pH electrode, an optical detector (SVO.sub.2), tissue impedance (electrical), or a strain gauge. Although only one sensor 80 is shown, multiple sensors 80 of the same or different type at the same or different locations may be utilized.
An example of an implantable blood pressure measurement device that may be disposed about a blood vessel is disclosed in U.S. Pat. No. 6,106,477 to Miesel et al., the entire disclosure of which is incorporated herein by reference. An example of a subcutaneous ECG monitor is available from Medtronic under the trade name REVEAL ILR and is disclosed in PCT Publication No. WO 98/02209, the entire disclosure of which is incorporated herein by reference. Other examples are disclosed in U.S. Pat. Nos. 5,987,352 and 5,331,966, the entire disclosures of which are incorporated herein by reference. Examples of devices and methods for measuring absolute blood pressure utilizing an ambient pressure reference are disclosed in U.S. Pat. No. 5,810,735 to Halperin et al., U.S. Pat. No. 5,904,708 to Goedeke, and PCT Publication No. WO 00/16686 to Brockway et al., the entire disclosures of which are incorporated herein by reference. The sensor 80 described herein may take the form of any of these devices or other devices that generally serve the same purpose.
The sensor 80 is preferably positioned in a chamber of the heart 11, or in/on a major artery such as the aortic arch 12, a common carotid artery 14/15, a subclavian artery 13/16 or the brachiocephalic artery 22, such that the parameter of interest may be readily ascertained. The sensor 80 may be disposed inside the body such as in or on an artery, a vein or a nerve (e.g. vagus nerve), or disposed outside the body, depending on the type of transducer or gauge utilized. The sensor 80 may be separate from the baroreceptor activation device 70 or combined therewith. For purposes of illustration only, the sensor 80 is shown positioned on the right subclavian artery 13.
By way of example, the control system 60 includes a control block 61 comprising a processor 63 and a memory 62. Control system 60 is connected to the sensor 80 by way of sensor cable 82. Control system 60 is also connected to the baroreceptor activation device 70 by way of electric control cable 72. Thus, the control system 60 receives a sensor signal from the sensor 80 by way of sensor cable 82, and transmits a control signal to the baroreceptor activation device 70 by way of control cable 72.
The system components 60/70/80 may be directly linked via cables 72/82 or by indirect means such as RF signal transceivers, ultrasonic transceivers or galvanic couplings. Examples of such indirect interconnection devices are disclosed in U.S. Pat. No. 4,987,897 to Funke and U.S. Pat. No. 5,113,859 to Funke, the entire disclosures of which are incorporated herein by reference.
The memory 62 may contain data related to the sensor signal, the control signal, and/or values and commands provided by the input device 64. The memory 62 may also include software containing one or more algorithms defining one or more functions or relationships between the control signal and the sensor signal. The algorithm may dictate activation or deactivation control signals depending on the sensor signal or a mathematical derivative thereof. The algorithm may dictate an activation or deactivation control signal when the sensor signal falls below a lower predetermined threshold value, rises above an upper predetermined threshold value or when the sensor signal indicates a specific physiologic event. The algorithm may dynamically alter the threshold value as determined by the sensor input values.
As mentioned previously, the baroreceptor activation device 70 activates baroreceptors 30 electrically, optionally in combination with mechanical, thermal, chemical, biological or other co-activation. In some instances, the control system 60 includes a driver 66 to provide the desired power mode for the baroreceptor activation device 70. For example, the driver 66 may comprise a power amplifier or the like and the cable 72 may comprise electrical lead(s). In other instances, the driver 66 may not be necessary, particularly if the processor 63 generates a sufficiently strong electrical signal for low level electrical actuation of the baroreceptor activation device 70.
The control system 60 may operate as a closed loop utilizing feedback from the sensor 80, or other sensors, such as heart rate sensors which may be incorporated or the electrode assembly, or as an open loop utilizing reprogramming commands received by input device 64. The closed loop operation of the control system 60 preferably utilizes some feedback from the transducer 80, but may also operate in an open loop mode without feedback. Programming commands received by the input device 64 may directly influence the control signal, the output activation parameters, or may alter the software and related algorithms contained in memory 62. The treating physician and/or patient may provide commands to input device 64. Display 65 may be used to view the sensor signal, control signal and/or the software/data contained in memory 62.
The control signal generated by the control system 60 may be continuous, periodic, alternating, episodic or a combination thereof, as dictated by an algorithm contained in memory 62. Continuous control signals include a constant pulse, a constant train of pulses, a triggered pulse and a triggered train of pulses. Examples of periodic control signals include each of the continuous control signals described above which have a designated start time (e.g., beginning of each period as designated by minutes, hours, or days in combinations of) and a designated duration (e.g., seconds, minutes, hours, or days in combinations of). Examples of alternating control signals include each of the continuous control signals as described above which alternate between the right and left output channels. Examples of episodic control signals include each of the continuous control signals described above which are triggered by an episode (e.g., activation by the physician/patient, an increase/decrease in blood pressure above a certain threshold, heart rate above/below certain levels, etc.).
The stimulus regimen governed by the control system 60 may be selected to promote long term efficacy. It is theorized that uninterrupted or otherwise unchanging activation of the baroreceptors 30 may result in the baroreceptors and/or the baroreflex system becoming less responsive over time, thereby diminishing the long term effectiveness of the therapy. Therefore, the stimulus regimen maybe selected to activate, deactivate or otherwise modulate the baroreceptor activation device 70 in such a way that therapeutic efficacy is maintained preferably for years.
In addition to maintaining therapeutic efficacy over time, the stimulus regimens of the present invention may be selected reduce power requirement/consumption of the system 60. As will be described in more detail hereinafter, the stimulus regimen may dictate that the baroreceptor activation device 70 be initially activated at a relatively higher energy and/or power level, and subsequently activated at a relatively lower energy and/or power level. The first level attains the desired initial therapeutic effect, and the second (lower) level sustains the desired therapeutic effect long term. By reducing the energy and/or power levels after the desired therapeutic effect is initially attained, the energy required or consumed by the activation device 70 is also reduced long term. This may correlate into systems having greater longevity and/or reduced size (due to reductions in the size of the power supply and associated components).
A first general approach for a stimulus regimen which promotes long term efficacy and reduces power requirements/consumption involves generating a control signal to cause the baroreceptor activation device 70 to have a first output level of relatively higher energy and/or power, and subsequently changing the control signal to cause the baroreceptor activation device 70 to have a second output level of relatively lower energy and/or power. The first output level may be selected and maintained for sufficient time to attain the desired initial effect (e.g., reduced heart rate and/or blood pressure), after which the output level may be reduced to the second level for sufficient time to sustain the desired effect for the desired period of time.
For example, if the first output level has a power and/or energy value of X1, the second output level may have a power and/or energy value of X2, wherein X2 is less than X1. In some instances, X2 may be equal to zero, such that the first level is “on” and the second level is “off”. It is recognized that power and energy refer to two different parameters, and in some cases, a change in one of the parameters (power or energy) may not correlate to the same or similar change in the other parameter. In the present invention, it is contemplated that a change in one or both of the parameters may be suitable to obtain the desired result of promoting long term efficacy.
It is also contemplated that more than two levels may be used. Each further level may increase the output energy or power to attain the desired effect, or decrease the output energy or power to retain the desired effect. For example, in some instances, it may be desirable to have further reductions in the output level if the desired effect may be sustained at lower power or energy levels. In other instances, particularly when the desired effect is diminishing or is otherwise not sustained, it may be desirable to increase the output level until the desired effect is reestablished, and subsequently decrease the output level to sustain the effect.
The transition from each level may be a step function (e.g., a single step or a series of steps), a gradual transition over a period of time, or a combination thereof. In addition, the signal levels may be continuous, periodic, alternating, or episodic as discussed previously.
In electrical activation using a non modulated signal, the output (power or energy) level of the baroreceptor activation device 70 may be changed by adjusting the output signal voltage level, current level and/or signal duration. The output signal of the baroreceptor activation device 70 may be, for example, constant current or constant voltage. In electrical activation embodiments using a modulated signal, wherein the output signal comprises, for example, a series of pulses, several pulse characteristics may be changed individually or in combination to change the power or energy level of the output signal. Such pulse characteristics include, but are not limited to: pulse amplitude (PA), pulse frequency (PF), pulse width or duration (PW), pulse waveform (square, triangular, sinusoidal, etc.), pulse polarity (for bipolar electrodes) and pulse phase (monophasic, biphasic).
In electrical activation wherein the output signal comprises a pulse train, several other signal characteristics may be changed in addition to the pulse characteristics described above, as described in copending application Ser. No. 09/964,079, the full disclosure of which is incorporated herein by reference.
Refer now to
The carotid sinus 20, and in particular the bulge 21 of the carotid sinus, may contain a relatively high density of baroreceptors 30 (not shown) in the vascular wall. For this reason, it may be desirable to position the electrodes 302 of the activation device 300 on and/or around the sinus bulge 21 to maximize baroreceptor responsiveness and to minimize extraneous tissue stimulation.
It should be understood that the device 300 and electrodes 302 are merely schematic, and only a portion of which may be shown, for purposes of illustrating various positions of the electrodes 302 on and/or around the carotid sinus 20 and the sinus bulge 21. In each of the embodiments described herein, the electrodes 302 may be monopolar, bipolar, or tripolar (anode-cathode-anode or cathode-anode-cathode sets). Specific extravascular electrode designs are described in more detail hereinafter.
The plurality of electrode pairs 302 may extend from a point proximal of the sinus 20 or bulge 21, to a point distal of the sinus 20 or bulge 21 to ensure activation of baroreceptors 30 throughout the sinus 20 region. The electrodes 302 may be connected to a single channel or multiple channels as discussed in more detail hereinafter. The plurality of electrode pairs 302 may be selectively activated for purposes of targeting a specific area of the sinus 20 to increase baroreceptor responsiveness, or for purposes of reducing the exposure of tissue areas to activation to maintain baroreceptor responsiveness long term.
From the foregoing discussion with reference to
For example, in
Refer now to
Base structure or substrate 306 may comprise a flexible and electrically insulating material suitable for implantation, such as silicone, perhaps reinforced with a flexible material such as polyester fabric. The base 306 may have a length suitable to wrap around all (360.degree.) or a portion (i.e., less than 360.degree.) of the circumference of one or more of the carotid arteries adjacent the carotid sinus 20. The electrodes 302 may extend around a portion (i.e., less than 360.degree. such as 270.degree., 180.degree. or 90.degree.) of the circumference of one or more of the carotid arteries adjacent the carotid sinus 20. To this end, the electrodes 302 may have a length that is less than (e.g., 75%, 50% or 25%) the length of the base 206. The electrodes 302 may be parallel, orthogonal or oblique to the length of the base 306, which is generally orthogonal to the axis of the carotid artery to which it is disposed about. Preferably, the base structure or backing will be elastic (i.e., stretchable), typically being composed of at least in part of silicone, latex, or other elastomer. If such elastic structures are reinforced, the reinforcement should be arranged so that it does not interfere with the ability of the base to stretch and conform to the vascular surface.
The electrodes 302 may comprise round wire, rectangular ribbon or foil formed of an electrically conductive and radiopaque material such as platinum. The base structure 306 substantially encapsulates the electrodes 302, leaving only an exposed area for electrical connection to extravascular carotid sinus tissue. For example, each electrode 302 may be partially recessed in the base 206 and may have one side exposed along all or a portion of its length for electrical connection to carotid tissue. Electrical paths through the carotid tissues may be defined by one or more pairs of the elongate electrodes 302.
In all embodiments described with reference to
An alternative multi-channel electrode design is illustrated in
A variation of the multi-channel pad type electrode design is illustrated in
Another variation of the multi-channel pad electrode design is illustrated in
For example, the control signal may comprise a pulse wave form, wherein each pulse includes a different code. The code for each pulse causes the chip 310 to enable one or more pairs of electrodes, and to disable the remaining electrodes. Thus, the pulse is only transmitted to the enabled electrode pair(s) corresponding to the code sent with that pulse. Each subsequent pulse would have a different code than the preceding pulse, such that the chip 310 enables and disables a different set of electrodes 302 corresponding to the different code. Thus, virtually any number of electrode pairs may be selectively activated using control chip 310, without the need for a separate channel in cable 304 for each electrode 302. By reducing the number of channels in cable 304, the size and cost thereof may be reduced.
Optionally, the IC chip 310 may be connected to feedback sensor 80, taking advantage of the same functions as described with reference to
Refer now to
In this embodiment, the base structure 306 of the activation device 300 may comprise molded tube, a tubular extrusion, or a sheet of material wrapped into a tube shape utilizing a suture flap 308 with sutures 309 as shown. The base structure 306 may be formed of a flexible and biocompatible material such as silicone, which may be reinforced with a flexible material such as polyester fabric available under the trade name DACRONŽ to form a composite structure. The inside diameter of the base structure 306 may correspond to the outside diameter of the carotid artery at the location of implantation, for example 6 to 8 mm. The wall thickness of the base structure 306 may be very thin to maintain flexibility and a low profile, for example less than 1 mm. If the device 300 is to be disposed about a sinus bulge 21, a correspondingly shaped bulge may be formed into the base structure for added support and assistance in positioning.
The electrodes 302 (shown in phantom) may comprise round wire, rectangular ribbon or foil, formed of an electrically conductive and radiopaque material such as platinum or platinum iridium. The electrodes may be molded into the base structure 306 or adhesively connected to the inside diameter thereof, leaving a portion of the electrode exposed for electrical connection to carotid tissues. The electrodes 302 may encompass less than the entire inside circumference (e.g., 300.degree.) of the base structure 306 to avoid shorting. The electrodes 302 may have any of the shapes and arrangements described previously. For example, as shown in
The support collar 312 may be formed similarly to base structure 306. For example, the support collar may comprise molded tube, a tubular extrusion, or a sheet of material wrapped into a tube shape utilizing a suture flap 315 with sutures 313 as shown. The support collar 312 may be formed of a flexible and biocompatible material such as silicone, which may be reinforced to form a composite structure. The cables 304 are secured to the support collar 312, leaving slack in the cables 304 between the support collar 312 and the activation device 300.
In all embodiments described herein, it may be desirable to secure the activation device to the vascular wall using sutures or other fixation means. For example, sutures 311 may be used to maintain the position of the electrical activation device 300 relative to the carotid anatomy (or other vascular site containing baroreceptors). Such sutures 311 may be connected to base structure 306, and pass through all or a portion of the vascular wall. For example, the sutures 311 may be threaded through the base structure 306, through the adventitia of the vascular wall, and tied. If the base structure 306 comprises a patch or otherwise partially surrounds the carotid anatomy, the corners and/or ends of the base structure may be sutured, with additional sutures evenly distributed therebetween. In order to minimize the propagation of a hole or a tear through the base structure 306, a reinforcement material such as polyester fabric may be embedded in the silicone material. In addition to sutures, other fixation means may be employed such as staples or a biocompatible adhesive, for example.
Refer now to
The ribs 316 of the activation device 300 are sized to fit about the carotid anatomy, such as the internal carotid artery 19 adjacent the carotid sinus 20. Similarly, the ribs 316 of the support collar 312 may be sized to fit about the carotid anatomy, such as the common carotid artery 14 proximal of the carotid sinus 20. The ribs 316 may be separated, placed on a carotid artery, and closed thereabout to secure the device 300 to the carotid anatomy.
Each of the ribs 316 of the device 300 includes an electrode 302 on the inside surface thereof for electrical connection to carotid tissues. The ribs 316 provide insulating material around the electrodes 302, leaving only an inside portion exposed to the vascular wall. The electrodes 302 are coupled to the multi-channel cable 304 through spine 317. Spine 317 also acts as a tether to ribs 316 of the support collar 312, which do not include electrodes since their function is to provide support. The multi-channel electrode 302 functions discussed with reference to
The ends of the ribs 316 may be connected (e.g., sutured) after being disposed about a carotid artery, or may remain open as shown. If the ends remain open, the ribs 316 may be formed of a relatively stiff material to ensure a mechanical lock around the carotid artery. For example, the ribs 316 may be formed of polyethylene, polypropylene, PTFE, or other similar insulating and biocompatible material. Alternatively, the ribs 316 may be formed of a metal such as stainless steel or a nickel titanium alloy, as long as the metallic material was electrically isolated from the electrodes 302. As a further alternative, the ribs 316 may comprise an insulating and biocompatible polymeric material with the structural integrity provided by metallic (e.g., stainless steel, nickel titanium alloy, etc.) reinforcement. In this latter alternative, the electrodes 302 may comprise the metallic reinforcement.
Refer now to
The electrodes 302 are connected to a modified bipolar endocardial pacing lead, available under the trade name CONIFIX from Innomedica (now BIOMEC Cardiovascular, Inc.), model number 501112. The proximal end of the cable 304 is connected to the control system 60 or driver 66 as described previously. The pacing lead is modified by removing the pacing electrode to form the cable body 304. The MP35 wires are extracted from the distal end thereof to form two coils 318 positioned side by side having a diameter of about 0.020 inches. The coils 318 are then attached to the electrodes utilizing 316 type stainless steel crimp terminals laser welded to one end of the platinum electrodes 302. The distal end of the cable 304 and the connection between the coils 318 and the ends of the electrodes 302 are encapsulated by silicone.
The cable 304 illustrated in
In this alternative embodiment, the cable body 304 may comprise two or more conductive wires 304 a arranged coaxially or collinearly as shown. Each conductive wire 304 a may comprise a multifilament structure of suitable conductive material such as stainless steel or MP35N. An insulating material may surround the wire conductors 304 a individually and/or collectively. For purposes of illustration only, a pair of electrically conductive wires 304 a having an insulating material surrounding each wire 304 a individually is shown. The insulated wires 304 a may be connected by a spacer 304 b comprising, for example, an insulating material. An additional jacket of suitable insulating material may surround each of the conductors 304 a. The insulating jacket may be formed to have the same curvilinear shape of the insulated wires 304 a to help maintain the shape of the cable body 304 during implantation.
If a sinusoidal configuration is chosen for the curvilinear shape, the amplitude (A) may range from 1 mm to 10 mm, and preferably ranges from 2 mm to 3 mm. The wavelength (WL) of the sinusoid may range from 2 mm to 20 mm, and preferably ranges from 4 mm to 10 mm. The curvilinear or sinusoidal shape may be formed by a heat setting procedure utilizing a fixture which holds the cable 304 in the desired shape while the cable is exposed to heat. Sufficient heat is used to heat set the conductive wires 304 a and/or the surrounding insulating material. After cooling, the cable 304 may be removed from the fixture, and the cable 304 retains the desired shape.
Refer now to
Alternatively, the transducer 750 may be adhesively connected to the wall of the artery 14 using a biologically compatible adhesive such as cyanoacrylate as shown in
Refer now to
As seen in
Each turn of the coil in the contact area of the electrodes 702/704 is exposed from the flexible support 706 and any adhesive to form a conductive path to the artery wall. The exposed electrodes 702/704 may have a length (e.g., 0.236 inches) sufficient to extend around at least a portion of the carotid sinus, for example. The electrode cuff 700 is assembled flat with the contact surfaces of the coil electrodes 702/704 tangent to the inside plane of the flexible support 706. When the electrode cuff 700 is wrapped around the artery, the inside contact surfaces of the coiled electrodes 702/704 are naturally forced to extend slightly above the adjacent surface of the flexible support, thereby improving contact to the artery wall.
The ratio of the diameter of the coiled electrodes 702/704 to the wire diameter is preferably large enough to allow the coil to bend and elongate without significant bending stress or torsional stress in the wire. Flexibility is a significant advantage of this design which allows the electrode cuff 700 to conform to the shape of the carotid artery and sinus, and permits expansion and contraction of the artery or sinus without encountering significant stress or fatigue. In particular, the flexible electrode cuff 700 may be wrapped around and stretched to conform to the shape of the carotid sinus and artery during implantation. This may be achieved without collapsing or distorting the shape of the artery and carotid sinus due to the compliance of the electrode cuff 700. The flexible support 706 is able to flex and stretch with the conductor coils 702/704 because of the absence of fabric reinforcement in the electrode contact portion of the cuff 700. By conforming to the artery shape, and by the edge of the flexible support 706 sealing against the artery wall, the amount of stray electrical field and extraneous stimulation will likely be reduced.
The pitch of the coil electrodes 702/704 may be greater than the wire diameter in order to provide a space between each turn of the wire to thereby permit bending without necessarily requiring axial elongation thereof. For example, the pitch of the contact coils 702/704 may be 0.004 inches per turn with a 0.002 inch diameter wire, which allows for a 0.002 inch space between the wires in each turn. The inside of the coil may be filled with a flexible adhesive material such as silicone adhesive which may fill the spaces between adjacent wire turns. By filling the small spaces between the adjacent coil turns, the chance of pinching tissue between coil turns is minimized thereby avoiding abrasion to the artery wall. Thus, the embedded coil electrodes 702/704 are mechanically captured and chemically bonded into the flexible support 706. In the unlikely event that a coil electrode 702/704 comes loose from the support 706, the diameter of the coil is large enough to be atraumatic to the artery wall. Preferably, the centerline of the coil electrodes 702/704 lie near the neutral axis of electrode cuff structure 700 and the flexible support 706 comprises a material with isotropic elasticity such as silicone in order to minimize the shear forces on the adhesive bonds between the coil electrodes 702/704 and the support 706.
The electrode coils 702/704 are connected to corresponding conductive coils 712/714, respectively, in an elongate lead 710 which is connected to the control system 60. Anchoring wings 718 may be provided on the lead 710 to tether the lead 710 to adjacent tissue and minimize the effects or relative movement between the lead 710 and the electrode cuff 700. As seen in
The conductive material of the electrodes 702/704 may be a metal as described above or a conductive polymer such as a silicone material filled with metallic particles such as Pt particles. In this latter embodiment, the polymeric electrodes may be integrally formed with the flexible support 706 with the electrode contacts comprising raised areas on the inside surface of the flexible support 706 electrically coupled to the lead 710 by wires or wire coils. The use of polymeric electrodes may be applied to other electrode design embodiments described elsewhere herein.
Reinforcement patches 708 such as DACRONŽ fabric may be selectively incorporated into the flexible support 706. For example, reinforcement patches 708 may be incorporated into the ends or other areas of the flexible support 706 to accommodate suture anchors. The reinforcement patches 708 provide points where the electrode cuff 700 may be sutured to the vessel wall and may also provide tissue in growth to further anchor the device 700 to the exterior of the vessel wall. For example, the fabric reinforcement patches 708 may extend beyond the edge of the flexible support 706 so that tissue in growth may help anchor the electrode assembly or cuff 700 to the vessel wall and may reduce reliance on the sutures to retain the electrode assembly 700 in place. As a substitute for or in addition to the sutures and tissue in growth, bioadhesives such as cyanoacrylate may be employed to secure the device 700 to the vessel wall. In addition, an adhesive incorporating conductive particles such as Pt coated micro spheres may be applied to the exposed inside surfaces of the electrodes 702/704 to enhance electrical conduction to the tissue and possibly limit conduction along one axis to limit extraneous tissue stimulation.
The reinforcement patches 708 may also be incorporated into the flexible support 706 for strain relief purposes and to help retain the coils 702/704 to the support 706 where the leads 710 attach to the electrode assembly 700 as well as where the outer coil 702 loops back around the inner coil 704. Preferably, the patches 708 are selectively incorporated into the flexible support 706 to permit expansion and contraction of the device 700, particularly in the area of the electrodes 702/704. In particular, the flexible support 706 is only fabric reinforced in selected areas thereby maintaining the ability of the electrode cuff 700 to stretch.
Referring now to
Referring now to
The geometry of the electrode assembly 900, and in particular the geometry of the base 902, is selected to permit a number of different attachment modes to the blood vessel. In particular, the geometry of the assembly 902 of
A number of reinforcement regions 910 (910 a, 910 b, 910 c, 910 d, and 910 e) are attached to different locations on the base 902 to permit suturing, clipping, stapling, or other fastening of the attachment tabs 906 to each other and/or the electrode-carrying surface 904 of the base 902. In the preferred embodiment intended for attachment at or around the carotid sinus, a first reinforcement strip 910 a is provided over an end of the base 902 opposite to the end which carries the attachment tabs. Pairs of reinforcement strips 910 b and 910 c are provided on each of the axially aligned attachment tabs 906 a and 906 b, while similar pairs of reinforcement strips 910 d and 910 e are provided on each of the transversely angled attachment tabs 906 c and 906 d. In the illustrated embodiment, all attachment tabs will be provided on one side of the base, preferably emanating from adjacent corners of the rectangular electrode-carrying surface 904.
The structure of electrode assembly 900 permits the surgeon to implant the electrode assembly so that the electrodes 920 (which are preferably stretchable, flat-coil electrodes as described in detail above), are located at a preferred location relative to the target baroreceptors. The preferred location may be determined, for example, as described in copending application Ser. No. 09/963,991, filed on Sep. 26, 2001, the full disclosure of which incorporated herein by reference.
Once the preferred location for the electrodes 920 of the electrode assembly 900 is determined, the surgeon may position the base 902 so that the electrodes 920 are located appropriately relative to the underlying baroreceptors. Thus, the electrodes 920 may be positioned over the common carotid artery CC as shown in
In other cases, the bulge of the carotid sinus and the baroreceptors may be located differently with respect to the carotid bifurcation. For example, as shown in
Refer now to
The local fluid delivery device 262 may include proximal and distal seals 266 which retain the fluid agent disposed in the lumen or cavity 268 adjacent to vascular wall. Preferably, the local fluid delivery device 262 completely surrounds the vascular wall 40 to maintain an effective seal. Those skilled in the art will recognize that the local fluid delivery device 262 may comprise a wide variety of implantable drug delivery devices or pumps known in the art.
The local fluid delivery device 260 is connected to a fluid line 264 which is connected to the driver 66 of the control system 60. In this embodiment, the driver 66 comprises a pressure/vacuum source and fluid reservoir containing the desired chemical or biological fluid agent. The chemical or biological fluid agent may comprise a wide variety of stimulatory substances. Examples include veratridine, bradykinin, prostaglandins, and related substances. Such stimulatory substances activate the baroreceptors 30 directly or enhance their sensitivity to other stimuli and therefore may be used in combination with the other baroreceptor activation devices described herein. Other examples include growth factors and other agents that modify the function of the baroreceptors 30 or the cells of the vascular tissue surrounding the baroreceptors 30 causing the baroreceptors 30 to be activated or causing alteration of their responsiveness or activation pattern to other stimuli.
In most activation device embodiments described herein, it may be desirable to incorporate anti-inflammatory agents (e.g., steroid eluting electrodes) such as described in U.S. Pat. No. 4,711,251 to Stokes, U.S. Pat. No. 5,522,874 to Gates and U.S. Pat. No. 4,972,848 to Di Domenico et al., the entire disclosures of which are incorporated herein by reference. Such agents reduce tissue inflammation at the chronic interface between the device (e.g., electrodes) and the vascular wall tissue, to thereby increase the efficiency of stimulus transfer, reduce power consumption, and maintain activation efficiency, for example.
Those skilled in the art will recognize that the present invention may be manifested in a variety of forms other than the specific embodiments described and contemplated herein. Accordingly, departures in form and detail may be made without departing from the scope and spirit of the present invention as described in the appended claims.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US3309924||22 Jun 1964||21 Mar 1967||Universtity Of California||Electromagnetic flow meter|
|US3421511||10 Dec 1965||14 Jan 1969||Medtronic Inc||Implantable electrode for nerve stimulation|
|US3522811||13 Feb 1969||4 Aug 1970||Medtronic Inc||Implantable nerve stimulator and method of use|
|US3593718||13 Jul 1967||20 Jul 1971||Biocybernetics Inc||Physiologically controlled cardiac pacer|
|US3645267||29 Oct 1969||29 Feb 1972||Medtronic Inc||Medical-electronic stimulator, particularly a carotid sinus nerve stimulator with controlled turn-on amplitude rate|
|US3650277||17 Feb 1970||21 Mar 1972||Lkb Medical Ab||Apparatus for influencing the systemic blood pressure in a patient by carotid sinus nerve stimulation|
|US3835864||21 Sep 1970||17 Sep 1974||Rasor Ass Inc||Intra-cardiac stimulator|
|US3870051||26 Apr 1973||11 Mar 1975||Nat Res Dev||Urinary control|
|US3943936||9 Oct 1973||16 Mar 1976||Rasor Associates, Inc.||Self powered pacers and stimulators|
|US4014318||22 May 1975||29 Mar 1977||Dockum James M||Circulatory assist device and system|
|US4256094||18 Jun 1979||17 Mar 1981||Kapp John P||Arterial pressure control system|
|US4323073||21 Aug 1979||6 Apr 1982||Cos Electronics Corporation||Apparatus and method for controlling the application of therapeutic direct current to living tissue|
|US4331157||9 Jul 1980||25 May 1982||Stimtech, Inc.||Mutually noninterfering transcutaneous nerve stimulation and patient monitoring|
|US4481953||29 Dec 1983||13 Nov 1984||Cordis Corporation||Endocardial lead having helically wound ribbon electrode|
|US4525074||14 Aug 1984||25 Jun 1985||Citizen Watch Co., Ltd.||Apparatus for measuring the quantity of physical exercise|
|US4531943||8 Aug 1983||30 Jul 1985||Angiomedics Corporation||Catheter with soft deformable tip|
|US4551862||15 Dec 1982||12 Nov 1985||Haber Terry M||Prosthetic sphincter|
|US4573481||25 Jun 1984||4 Mar 1986||Huntington Institute Of Applied Research||Implantable electrode array|
|US4586501||19 Oct 1983||6 May 1986||Michel Claracq||Device for partly occluding a vessel in particular the inferior vena cava and inherent component of this device|
|US4590946||14 Jun 1984||27 May 1986||Biomed Concepts, Inc.||Surgically implantable electrode for nerve bundles|
|US4628942||11 Oct 1984||16 Dec 1986||Case Western Reserve University||Asymmetric shielded two electrode cuff|
|US4640286||2 Nov 1984||3 Feb 1987||Staodynamics, Inc.||Optimized nerve fiber stimulation|
|US4641664||15 Apr 1985||10 Feb 1987||Siemens Aktiengesellschaft||Endocardial electrode arrangement|
|US4664120||22 Jan 1986||12 May 1987||Cordis Corporation||Adjustable isodiametric atrial-ventricular pervenous lead|
|US4682583||13 Apr 1984||28 Jul 1987||Burton John H||Inflatable artificial sphincter|
|US4702254||30 Dec 1985||27 Oct 1987||Jacob Zabara||Neurocybernetic prosthesis|
|US4709690||21 Apr 1986||1 Dec 1987||Habley Medical Technology Corporation||Implantable blood flow and occlusion pressure sensing sphincteric system|
|US4711251||31 Mar 1983||8 Dec 1987||Medtronic, Inc.||Body implantable lead|
|US4719921||28 Aug 1985||19 Jan 1988||Raul Chirife||Cardiac pacemaker adaptive to physiological requirements|
|US4739762||3 Nov 1986||26 Apr 1988||Expandable Grafts Partnership||Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft|
|US4762130||15 Jan 1987||9 Aug 1988||Thomas J. Fogarty||Catheter with corkscrew-like balloon|
|US4762820||3 Mar 1986||9 Aug 1988||Trustees Of Boston University||Therapeutic treatment for congestive heart failure|
|US4770177||18 Feb 1986||13 Sep 1988||Telectronics N.V.||Apparatus and method for adjusting heart/pacer relative to changes in venous diameter during exercise to obtain a required cardiac output.|
|US4791931||13 Aug 1987||20 Dec 1988||Pacesetter Infusion, Ltd.||Demand pacemaker using an artificial baroreceptor reflex|
|US4800882||13 Mar 1987||31 Jan 1989||Cook Incorporated||Endovascular stent and delivery system|
|US4803988||2 Feb 1987||14 Feb 1989||Staodynamics, Inc.||Nerve fiber stimulation using plural equally active electrodes|
|US4813418||2 Feb 1987||21 Mar 1989||Staodynamics, Inc.||Nerve fiber stimulation using symmetrical biphasic waveform applied through plural equally active electrodes|
|US4819662||26 Oct 1987||11 Apr 1989||Cardiac Pacemakers, Inc.||Cardiac electrode with drug delivery capabilities|
|US4825871||18 May 1987||2 May 1989||Societe Anonyme Dite: Atesys||Defibrillating or cardioverting electric shock system including electrodes|
|US4828544||5 Sep 1985||9 May 1989||Quotidian No. 100 Pty Limited||Control of blood flow|
|US4830003||17 Jun 1988||16 May 1989||Wolff Rodney G||Compressive stent and delivery system|
|US4832038||20 Jan 1987||23 May 1989||The Board Of Trustees Of University Of Illinois||Apparatus for monitoring cardiovascular regulation using heart rate power spectral analysis|
|US4860751||4 Feb 1985||29 Aug 1989||Cordis Corporation||Activity sensor for pacemaker control|
|US4862361||5 Jun 1985||29 Aug 1989||Massachusetts Institute Of Technology||Methods and apparatus for monitoring cardiovascular regulation using heart rate power spectral analysis|
|US4867164||26 Oct 1987||19 Sep 1989||Jacob Zabara||Neurocybernetic prosthesis|
|US4881939||19 Feb 1985||21 Nov 1989||The Johns Hopkins University||Implantable helical cuff|
|US4886062||19 Oct 1987||12 Dec 1989||Medtronic, Inc.||Intravascular radially expandable stent and method of implant|
|US4887608||10 Jan 1989||19 Dec 1989||Boston Scientific Corporation||Method and apparatus for estimating tissue damage|
|US4915113||16 Dec 1988||10 Apr 1990||Bio-Vascular, Inc.||Method and apparatus for monitoring the patency of vascular grafts|
|US4917092||13 Jul 1988||17 Apr 1990||Medical Designs, Inc.||Transcutaneous nerve stimulator for treatment of sympathetic nerve dysfunction|
|US4926875||26 May 1988||22 May 1990||Baylor College Of Medicine||Implantable and extractable biological sensor probe|
|US4930517||25 Apr 1989||5 Jun 1990||Massachusetts Institute Of Technology||Method and apparatus for physiologic system identification|
|US4934368||21 Jan 1988||19 Jun 1990||Myo/Kinetics Systems, Inc.||Multi-electrode neurological stimulation apparatus|
|US4940065||23 Jan 1989||10 Jul 1990||Regents Of The University Of California||Surgically implantable peripheral nerve electrode|
|US4960129||5 Dec 1988||2 Oct 1990||Trustees Of The University Of Pennsylvania||Methods of observing autonomic neural stimulation and diagnosing cardiac dynamical dysfunction using heartbeat interval data to analyze cardioventilatory interactions|
|US4960133||21 Nov 1988||2 Oct 1990||Brunswick Manufacturing Co., Inc.||Esophageal electrode|
|US4967159||23 Feb 1989||30 Oct 1990||Abbott Laboratories||Self-balancing reflectometer|
|US4969458||6 Jul 1987||13 Nov 1990||Medtronic, Inc.||Intracoronary stent and method of simultaneous angioplasty and stent implant|
|US4972848||23 Aug 1989||27 Nov 1990||Medtronic, Inc.||Medical electrical lead with polymeric monolithic controlled release device and method of manufacture|
|US4987897||18 Sep 1989||29 Jan 1991||Medtronic, Inc.||Body bus medical device communication system|
|US5010893||24 Mar 1988||30 Apr 1991||Siemens-Pacesetter, Inc.||Motion sensor for implanted medical device|
|US5025807||25 Jan 1989||25 Jun 1991||Jacob Zabara||Neurocybernetic prosthesis|
|US5031621||6 Dec 1989||16 Jul 1991||Grandjean Pierre A||Nerve electrode with biological substrate|
|US5040533||29 Dec 1989||20 Aug 1991||Medical Engineering And Development Institute Incorporated||Implantable cardiovascular treatment device container for sensing a physiological parameter|
|US5078736||4 May 1990||7 Jan 1992||Interventional Thermodynamics, Inc.||Method and apparatus for maintaining patency in the body passages|
|US5086787||28 Feb 1991||11 Feb 1992||Medtronic, Inc.||Steroid eluting intramuscular lead|
|US5092332||22 Feb 1990||3 Mar 1992||Medtronic, Inc.||Steroid eluting cuff electrode for peripheral nerve stimulation|
|US5111815||15 Oct 1990||12 May 1992||Cardiac Pacemakers, Inc.||Method and apparatus for cardioverter/pacer utilizing neurosensing|
|US5113859||25 Jun 1990||19 May 1992||Medtronic, Inc.||Acoustic body bus medical device communication system|
|US5113869||21 Aug 1990||19 May 1992||Telectronics Pacing Systems, Inc.||Implantable ambulatory electrocardiogram monitor|
|US5117826||2 May 1991||2 Jun 1992||Staodyn, Inc.||Combined nerve fiber and body tissue stimulation apparatus and method|
|US5134997||14 Aug 1990||4 Aug 1992||Medtronic, Inc.||Rate responsive pacemaker and pacing method|
|US5144960||20 Mar 1991||8 Sep 1992||Medtronic, Inc.||Transvenous defibrillation lead and method of use|
|US5154170||14 Aug 1990||13 Oct 1992||Medtronic, Inc.||Optimization for rate responsive cardiac pacemaker|
|US5154182||15 Feb 1991||13 Oct 1992||Siemens Pacesetter, Inc.||Drug or steroid releasing patch electrode for an implantable arrhythmia treatment system|
|US5158078||14 Aug 1990||27 Oct 1992||Medtronic, Inc.||Rate responsive pacemaker and methods for optimizing its operation|
|US5170802||7 Jan 1991||15 Dec 1992||Medtronic, Inc.||Implantable electrode for location within a blood vessel|
|US5181911||22 Apr 1991||26 Jan 1993||Shturman Technologies, Inc.||Helical balloon perfusion angioplasty catheter|
|US5199428||22 Mar 1991||6 Apr 1993||Medtronic, Inc.||Implantable electrical nerve stimulator/pacemaker with ischemia for decreasing cardiac workload|
|US5203326||18 Dec 1991||20 Apr 1993||Telectronics Pacing Systems, Inc.||Antiarrhythmia pacer using antiarrhythmia pacing and autonomic nerve stimulation therapy|
|US5215089||21 Oct 1991||1 Jun 1993||Cyberonics, Inc.||Electrode assembly for nerve stimulation|
|US5222971||9 Oct 1990||29 Jun 1993||Scimed Life Systems, Inc.||Temporary stent and methods for use and manufacture|
|US5224491||30 Jun 1992||6 Jul 1993||Medtronic, Inc.||Implantable electrode for location within a blood vessel|
|US5243980||30 Jun 1992||14 Sep 1993||Medtronic, Inc.||Method and apparatus for discrimination of ventricular and supraventricular tachycardia|
|US5247945||13 Jun 1991||28 Sep 1993||Siemens Aktiengesellschaft||Electrode arrangement for a defibrillator|
|US5259394||23 Dec 1991||9 Nov 1993||Ela Medical||Endocardiac lead having an active fastening means|
|US5265608||5 Dec 1991||30 Nov 1993||Medtronic, Inc.||Steroid eluting electrode for peripheral nerve stimulation|
|US5269303||22 Feb 1991||14 Dec 1993||Cyberonics, Inc.||Treatment of dementia by nerve stimulation|
|US5282468||8 Jan 1992||1 Feb 1994||Medtronic, Inc.||Implantable neural electrode|
|US5282844||18 May 1992||1 Feb 1994||Medtronic, Inc.||High impedance, low polarization, low threshold miniature steriod eluting pacing lead electrodes|
|US5295959||13 Mar 1992||22 Mar 1994||Medtronic, Inc.||Autoperfusion dilatation catheter having a bonded channel|
|US5299569||3 May 1991||5 Apr 1994||Cyberonics, Inc.||Treatment of neuropsychiatric disorders by nerve stimulation|
|US5304206||18 Nov 1991||19 Apr 1994||Cyberonics, Inc.||Activation techniques for implantable medical device|
|US5305745 *||2 Apr 1992||26 Apr 1994||Fred Zacouto||Device for protection against blood-related disorders, notably thromboses, embolisms, vascular spasms, hemorrhages, hemopathies and the presence of abnormal elements in the blood|
|US5314453||6 Dec 1991||24 May 1994||Spinal Cord Society||Position sensitive power transfer antenna|
|US5318592||14 Sep 1992||7 Jun 1994||BIOTRONIK, Mess- und Therapiegerate GmbH & Co., Ingenieurburo Berlin||Cardiac therapy system|
|US5324310||1 Jul 1992||28 Jun 1994||Medtronic, Inc.||Cardiac pacemaker with auto-capture function|
|US5324325||29 Mar 1993||28 Jun 1994||Siemens Pacesetter, Inc.||Myocardial steroid releasing lead|
|US5325870||16 Dec 1992||5 Jul 1994||Angeion Corporation||Multiplexed defibrillation electrode apparatus|
|US5330507||24 Apr 1992||19 Jul 1994||Medtronic, Inc.||Implantable electrical vagal stimulation for prevention or interruption of life threatening arrhythmias|
|US5330515||17 Jun 1992||19 Jul 1994||Cyberonics, Inc.||Treatment of pain by vagal afferent stimulation|
|US5331966||16 Dec 1993||26 Jul 1994||Medtronic, Inc.||Subcutaneous multi-electrode sensing system, method and pacer|
|US5335657||3 May 1991||9 Aug 1994||Cyberonics, Inc.||Therapeutic treatment of sleep disorder by nerve stimulation|
|US5351394||21 Sep 1992||4 Oct 1994||Cyberonics, Inc.||Method of making a nerve electrode array|
|US5358514||17 May 1993||25 Oct 1994||Alfred E. Mann Foundation For Scientific Research||Implantable microdevice with self-attaching electrodes|
|US5387234||19 May 1993||7 Feb 1995||Siemens-Elema Ab||Medical electrode device|
|US5408744||30 Apr 1993||25 Apr 1995||Medtronic, Inc.||Substrate for a sintered electrode|
|US5411535||2 Mar 1993||2 May 1995||Terumo Kabushiki Kaisha||Cardiac pacemaker using wireless transmission|
|US5411540||3 Jun 1993||2 May 1995||Massachusetts Institute Of Technology||Method and apparatus for preferential neuron stimulation|
|US5431171||25 Jun 1993||11 Jul 1995||The Regents Of The University Of California||Monitoring fetal characteristics by radiotelemetric transmission|
|US5437285||30 Nov 1993||1 Aug 1995||Georgetown University||Method and apparatus for prediction of sudden cardiac death by simultaneous assessment of autonomic function and cardiac electrical stability|
|US5458626||27 Dec 1993||17 Oct 1995||Krause; Horst E.||Method of electrical nerve stimulation for acceleration of tissue healing|
|US5507784||6 Apr 1995||16 Apr 1996||Medtronic, Inc.||Method and apparatus for control of A-V interval|
|US5509888||26 Jul 1994||23 Apr 1996||Conceptek Corporation||Controller valve device and method|
|US5522854||19 May 1994||4 Jun 1996||Duke University||Method and apparatus for the prevention of arrhythmia by nerve stimulation|
|US5522874||28 Jul 1994||4 Jun 1996||Gates; James T.||Medical lead having segmented electrode|
|US5529067||19 Aug 1994||25 Jun 1996||Novoste Corporation||Methods for procedures related to the electrophysiology of the heart|
|US5531766||23 Jan 1995||2 Jul 1996||Angeion Corporation||Implantable cardioverter defibrillator pulse generator kite-tail electrode system|
|US5531778||20 Sep 1994||2 Jul 1996||Cyberonics, Inc.||Circumneural electrode assembly|
|US5531779||24 Jan 1995||2 Jul 1996||Cardiac Pacemakers, Inc.||Stent-type defibrillation electrode structures|
|US5535752||27 Feb 1995||16 Jul 1996||Medtronic, Inc.||Implantable capacitive absolute pressure and temperature monitor system|
|US5540734||28 Sep 1994||30 Jul 1996||Zabara; Jacob||Cranial nerve stimulation treatments using neurocybernetic prosthesis|
|US5540735||12 Dec 1994||30 Jul 1996||Rehabilicare, Inc.||Apparatus for electro-stimulation of flexing body portions|
|US5545132||21 Dec 1993||13 Aug 1996||C. R. Bard, Inc.||Helically grooved balloon for dilatation catheter and method of using|
|US5545202||4 Aug 1994||13 Aug 1996||Cardiac Pacemakers, Inc.||Body implantable defibrillation system|
|US5551953||31 Oct 1994||3 Sep 1996||Alza Corporation||Electrotransport system with remote telemetry link|
|US5571150||19 Dec 1994||5 Nov 1996||Cyberonics, Inc.||Treatment of patients in coma by nerve stimulation|
|US5575809||11 Jun 1993||19 Nov 1996||Kabushiki Kaisya Advance||Electrical stimulator|
|US5578061||3 Oct 1995||26 Nov 1996||Pacesetter Ab||Method and apparatus for cardiac therapy by stimulation of a physiological representative of the parasympathetic nervous system|
|US5593431||30 Mar 1995||14 Jan 1997||Medtronic, Inc.||Medical service employing multiple DC accelerometers for patient activity and posture sensing and method|
|US5634878||19 Sep 1994||3 Jun 1997||Eska Medical Gmbh & Co.||Implantable device for selectively opening and closing a tubular organ of the body|
|US5643330||12 Feb 1996||1 Jul 1997||Medtronic, Inc.||Multichannel apparatus for epidural spinal cord stimulation|
|US5645570||17 Jun 1994||8 Jul 1997||Sorin Biomedica S.P.A.||Method and device for monitoring and detecting sympatho-vagal activity and for providing therapy in response thereto|
|US5651378||20 Feb 1996||29 Jul 1997||Cardiothoracic Systems, Inc.||Method of using vagal nerve stimulation in surgery|
|US5680590||5 Sep 1995||21 Oct 1997||Parti; Michael||Simulation system and method of using same|
|US5683430||16 Nov 1995||4 Nov 1997||Ael Industries, Inc.||Status monitor for anomaly detection in implanted devices and method|
|US5690681||29 Mar 1996||25 Nov 1997||Purdue Research Foundation||Method and apparatus using vagal stimulation for control of ventricular rate during atrial fibrillation|
|US5692882||22 May 1996||2 Dec 1997||The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration||Axial pump|
|US5694939||3 Oct 1995||9 Dec 1997||The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration||Autogenic-feedback training exercise (AFTE) method and system|
|US5695468||16 Jan 1996||9 Dec 1997||Scimed Life Systems, Inc.||Balloon catheter with improved pressure source|
|US5700282||13 Oct 1995||23 Dec 1997||Zabara; Jacob||Heart rhythm stabilization using a neurocybernetic prosthesis|
|US5707400||19 Sep 1995||13 Jan 1998||Cyberonics, Inc.||Treating refractory hypertension by nerve stimulation|
|US5715837||29 Aug 1996||10 Feb 1998||Light Sciences Limited Partnership||Transcutaneous electromagnetic energy transfer|
|US5725471||28 Nov 1994||10 Mar 1998||Neotonus, Inc.||Magnetic nerve stimulator for exciting peripheral nerves|
|US5725563||20 Apr 1994||10 Mar 1998||Klotz; Antoine||Electronic device and method for adrenergically stimulating the sympathetic system with respect to the venous media|
|US5727558||14 Feb 1996||17 Mar 1998||Hakki; A-Hamid||Noninvasive blood pressure monitor and control device|
|US5741316||2 Dec 1996||21 Apr 1998||Light Sciences Limited Partnership||Electromagnetic coil configurations for power transmission through tissue|
|US5766236||19 Apr 1996||16 Jun 1998||Detty; Gerald D.||Electrical stimulation support braces|
|US5766527||10 Apr 1996||16 Jun 1998||Medtronic, Inc.||Method of manufacturing medical electrical lead|
|US5775331||7 Jun 1995||7 Jul 1998||Uromed Corporation||Apparatus and method for locating a nerve|
|US5776178||21 Feb 1996||7 Jul 1998||Medtronic, Inc.||Medical electrical lead with surface treatment for enhanced fixation|
|US5782891||15 Apr 1996||21 Jul 1998||Medtronic, Inc.||Implantable ceramic enclosure for pacing, neurological, and other medical applications in the human body|
|US5800464||3 Oct 1996||1 Sep 1998||Medtronic, Inc.||System for providing hyperpolarization of cardiac to enhance cardiac function|
|US5807258||14 Oct 1997||15 Sep 1998||Cimochowski; George E.||Ultrasonic sensors for monitoring the condition of a vascular graft|
|US5810735||1 May 1997||22 Sep 1998||Medtronic, Inc.||External patient reference sensors|
|US5814079||4 Oct 1996||29 Sep 1998||Medtronic, Inc.||Cardiac arrhythmia management by application of adnodal stimulation for hyperpolarization of myocardial cells|
|US5814089||18 Dec 1996||29 Sep 1998||Medtronic, Inc.||Leadless multisite implantable stimulus and diagnostic system|
|US5824021||22 Jul 1997||20 Oct 1998||Medtronic Inc.||Method and apparatus for providing feedback to spinal cord stimulation for angina|
|US5853652||14 Oct 1994||29 Dec 1998||Medtronic, Inc.||Method of manufacturing a medical electrical lead|
|US5861012||18 Oct 1996||19 Jan 1999||Medtronic, Inc.||Atrial and ventricular capture detection and threshold-seeking pacemaker|
|US5861015||5 May 1997||19 Jan 1999||Benja-Athon; Anuthep||Modulation of the nervous system for treatment of pain and related disorders|
|US5876422||7 Jul 1998||2 Mar 1999||Vitatron Medical B.V.||Pacemaker system with peltier cooling of A-V node for treating atrial fibrillation|
|US5891181||15 Sep 1997||6 Apr 1999||Zhu; Qiang||Blood pressure depressor|
|US5895416||12 Mar 1997||20 Apr 1999||Medtronic, Inc.||Method and apparatus for controlling and steering an electric field|
|US5904708||19 Mar 1998||18 May 1999||Medtronic, Inc.||System and method for deriving relative physiologic signals|
|US5913876||22 Sep 1997||22 Jun 1999||Cardiothoracic Systems, Inc.||Method and apparatus for using vagus nerve stimulation in surgery|
|US5916239||24 Nov 1997||29 Jun 1999||Purdue Research Foundation||Method and apparatus using vagal stimulation for control of ventricular rate during atrial fibrillation|
|US5919220||8 Sep 1995||6 Jul 1999||Fraunhofer Gesellschaft Zur Foerderung Der Angewandten Forschung E.V.||Cuff electrode|
|US5928272||2 May 1998||27 Jul 1999||Cyberonics, Inc.||Automatic activation of a neurostimulator device using a detection algorithm based on cardiac activity|
|US5938596||17 Mar 1997||17 Aug 1999||Medtronic, Inc.||Medical electrical lead|
|US5954761||25 Mar 1997||21 Sep 1999||Intermedics Inc.||Implantable endocardial lead assembly having a stent|
|US5967986||25 Nov 1997||19 Oct 1999||Vascusense, Inc.||Endoluminal implant with fluid flow sensing capability|
|US5967989||15 May 1998||19 Oct 1999||Vascusense, Inc.||Ultrasonic sensors for monitoring the condition of a vascular graft|
|US5987352||3 Mar 1998||16 Nov 1999||Medtronic, Inc.||Minimally invasive implantable device for monitoring physiologic events|
|US5987746||21 Feb 1996||23 Nov 1999||Medtronic, Inc.||Method of making medical electrical lead|
|US5989230||10 Feb 1997||23 Nov 1999||Essex Technology, Inc.||Rotate to advance catheterization system|
|US5991667||10 Nov 1997||23 Nov 1999||Vitatron Medical, B.V.||Pacing lead with porous electrode for stable low threshold high impedance pacing|
|US6006134||30 Apr 1998||21 Dec 1999||Medtronic, Inc.||Method and device for electronically controlling the beating of a heart using venous electrical stimulation of nerve fibers|
|US6016449||27 Oct 1997||18 Jan 2000||Neuropace, Inc.||System for treatment of neurological disorders|
|US6023642||8 May 1997||8 Feb 2000||Biogenics Ii, Llc||Compact transcutaneous electrical nerve stimulator|
|US6050952||14 Jan 1998||18 Apr 2000||Hakki; A-Hamid||Method for noninvasive monitoring and control of blood pressure|
|US6052623||30 Nov 1998||18 Apr 2000||Medtronic, Inc.||Feedthrough assembly for implantable medical devices and methods for providing same|
|US6058331||27 Apr 1998||2 May 2000||Medtronic, Inc.||Apparatus and method for treating peripheral vascular disease and organ ischemia by electrical stimulation with closed loop feedback control|
|US6061596||20 Nov 1996||9 May 2000||Advanced Bionics Corporation||Method for conditioning pelvic musculature using an implanted microstimulator|
|US6073048||17 Nov 1995||6 Jun 2000||Medtronic, Inc.||Baroreflex modulation with carotid sinus nerve stimulation for the treatment of heart failure|
|US6077227||28 Dec 1998||20 Jun 2000||Medtronic, Inc.||Method for manufacture and implant of an implantable blood vessel cuff|
|US6077298||20 Feb 1999||20 Jun 2000||Tu; Lily Chen||Expandable/retractable stent and methods thereof|
|US6104956||30 May 1997||15 Aug 2000||Board Of Trustees Of Southern Illinois University||Methods of treating traumatic brain injury by vagus nerve stimulation|
|US6106477||28 Dec 1998||22 Aug 2000||Medtronic, Inc.||Chronically implantable blood vessel cuff with sensor|
|US6110098||18 Dec 1996||29 Aug 2000||Medtronic, Inc.||System and method of mechanical treatment of cardiac fibrillation|
|US6115628||29 Mar 1999||5 Sep 2000||Medtronic, Inc.||Method and apparatus for filtering electrocardiogram (ECG) signals to remove bad cycle information and for use of physiologic signals determined from said filtered ECG signals|
|US6115630||29 Mar 1999||5 Sep 2000||Medtronic, Inc.||Determination of orientation of electrocardiogram signal in implantable medical devices|
|US6128526||29 Mar 1999||3 Oct 2000||Medtronic, Inc.||Method for ischemia detection and apparatus for using same|
|US6141588||24 Jul 1998||31 Oct 2000||Intermedics Inc.||Cardiac simulation system having multiple stimulators for anti-arrhythmia therapy|
|US6141590||25 Sep 1997||31 Oct 2000||Medtronic, Inc.||System and method for respiration-modulated pacing|
|US6161029||8 Mar 1999||12 Dec 2000||Medtronic, Inc.||Apparatus and method for fixing electrodes in a blood vessel|
|US6161047||30 Apr 1998||12 Dec 2000||Medtronic Inc.||Apparatus and method for expanding a stimulation lead body in situ|
|US6178349||15 Apr 1999||23 Jan 2001||Medtronic, Inc.||Drug delivery neural stimulation device for treatment of cardiovascular disorders|
|US6178352||7 May 1999||23 Jan 2001||Woodside Biomedical, Inc.||Method of blood pressure moderation|
|US6193996||25 Mar 1999||27 Feb 2001||3M Innovative Properties Company||Device for the transdermal delivery of diclofenac|
|US6205359||26 Oct 1998||20 Mar 2001||Birinder Bob Boveja||Apparatus and method for adjunct (add-on) therapy of partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator|
|US6206914||31 Aug 1998||27 Mar 2001||Medtronic, Inc.||Implantable system with drug-eluting cells for on-demand local drug delivery|
|US6208894||25 Mar 1998||27 Mar 2001||Alfred E. Mann Foundation For Scientific Research And Advanced Bionics||System of implantable devices for monitoring and/or affecting body parameters|
|US6231516||23 Feb 1998||15 May 2001||Vacusense, Inc.||Endoluminal implant with therapeutic and diagnostic capability|
|US6253110||27 Apr 1999||26 Jun 2001||Medtronic Inc||Method for tissue stimulation and fabrication of low polarization implantable stimulation electrode|
|US6255296||30 Apr 1999||3 Jul 2001||Endomatrix, Inc.||Composition and method for treating a patient susceptible to or suffering from a cardiovascular disorder or disease|
|US6266564||3 Nov 1999||24 Jul 2001||Medtronic, Inc.||Method and device for electronically controlling the beating of a heart|
|US6292695||17 Jun 1999||18 Sep 2001||Wilton W. Webster, Jr.||Method and apparatus for transvascular treatment of tachycardia and fibrillation|
|US6292703||8 Oct 1999||18 Sep 2001||Biotronik Mess-Und Therapiegerate Gmbh & Co.||Neural electrode arrangement|
|US6324421||29 Mar 1999||27 Nov 2001||Medtronic, Inc.||Axis shift analysis of electrocardiogram signal parameters especially applicable for multivector analysis by implantable medical devices, and use of same|
|US6341236||30 Apr 1999||22 Jan 2002||Ivan Osorio||Vagal nerve stimulation techniques for treatment of epileptic seizures|
|US6371922||7 Apr 2000||16 Apr 2002||Cardiac Pacemakers, Inc.||Method for measuring baroreflex sensitivity and therapy optimization in heart failure patients|
|US6393324||22 Jan 2001||21 May 2002||Woodside Biomedical, Inc.||Method of blood pressure moderation|
|US6397109||29 Dec 1999||28 May 2002||Avio Maria Perna||Single pass multiple chamber implantable electro-catheter for multi-site electrical therapy of up to four cardiac chambers, indicated in the treatment of such pathologies as atrial fibrillation and congestive/dilate cardio myopathy|
|US6401129||5 May 2000||4 Jun 2002||Telefonaktiebolaget Lm Ericsson (Publ)||Routing functionality application in a data communications network with a number of hierarchical nodes|
|US6415183||9 Dec 1999||2 Jul 2002||Cardiac Pacemakers, Inc.||Method and apparatus for diaphragmatic pacing|
|US6438409||24 Mar 2000||20 Aug 2002||Medtronic, Inc.||Methods of characterizing ventricular operations and applications thereof|
|US6438428||27 Oct 1999||20 Aug 2002||Axelgaard Manufacturing Co., Ltd.||Electrical stimulation compress|
|US6442413||15 May 2000||27 Aug 2002||James H. Silver||Implantable sensor|
|US6442435||21 May 2001||27 Aug 2002||Medtronic, Inc.||Apparatus and method for expanding a stimulation lead body in situ|
|US6445953||16 Jan 2001||3 Sep 2002||Kenergy, Inc.||Wireless cardiac pacing system with vascular electrode-stents|
|US6473644||13 Oct 1999||29 Oct 2002||Cyberonics, Inc.||Method to enhance cardiac capillary growth in heart failure patients|
|US6522926||27 Sep 2000||18 Feb 2003||Cvrx, Inc.||Devices and methods for cardiovascular reflex control|
|US6564101||2 Feb 1999||13 May 2003||The Trustees Of Columbia University In The City Of New York||Electrical system for weight loss and laparoscopic implanation thereof|
|US6564102||19 Apr 2001||13 May 2003||Birinder R. Boveja||Apparatus and method for adjunct (add-on) treatment of coma and traumatic brain injury with neuromodulation using an external stimulator|
|US6584362||30 Aug 2000||24 Jun 2003||Cardiac Pacemakers, Inc.||Leads for pacing and/or sensing the heart from within the coronary veins|
|US6600956||21 Aug 2001||29 Jul 2003||Cyberonics, Inc.||Circumneural electrode assembly|
|US6611713||30 Nov 2000||26 Aug 2003||Patrick Schauerte||Implantable device for diagnosing and distinguishing supraventricular and ventricular tachycardias|
|US6622041||21 Aug 2001||16 Sep 2003||Cyberonics, Inc.||Treatment of congestive heart failure and autonomic cardiovascular drive disorders|
|US6626839||29 Oct 2001||30 Sep 2003||Transoma Medical, Inc.||Respiration monitoring system based on sensed physiological parameters|
|US6666826||4 Jan 2002||23 Dec 2003||Cardiac Pacemakers, Inc.||Method and apparatus for measuring left ventricular pressure|
|US6668191||19 Apr 2001||23 Dec 2003||Birinder R. Boveja||Apparatus and method for electrical stimulation adjunct (add-on) therapy of atrial fibrillation, inappropriate sinus tachycardia, and refractory hypertension with an external stimulator|
|US6669645||15 Oct 2002||30 Dec 2003||Colin Corporation||Autonomic-nerve-function evaluating apparatus|
|US6671556||9 Nov 2001||30 Dec 2003||Ivan Osorio||Vagal nerve stimulation techniques for treatment of epileptic seizures|
|US6701176||29 Oct 1999||2 Mar 2004||Johns Hopkins University School Of Medicine||Magnetic-resonance-guided imaging, electrophysiology, and ablation|
|US6701186||13 Sep 2001||2 Mar 2004||Cardiac Pacemakers, Inc.||Atrial pacing and sensing in cardiac resynchronization therapy|
|US6704598||23 May 2001||9 Mar 2004||Cardiac Pacemakers, Inc.||Cardiac rhythm management system selecting between multiple same-chamber electrodes for delivering cardiac therapy|
|US6718212||12 Oct 2001||6 Apr 2004||Medtronic, Inc.||Implantable medical electrical lead with light-activated adhesive fixation|
|US6748272||18 May 2001||8 Jun 2004||Cardiac Pacemakers, Inc.||Atrial interval based heart rate variability diagnostic for cardiac rhythm management system|
|US6766189||30 Mar 2001||20 Jul 2004||Cardiac Pacemakers, Inc.||Method and apparatus for predicting acute response to cardiac resynchronization therapy|
|US6768923||5 Dec 2001||27 Jul 2004||Cardiac Pacemakers, Inc.||Apparatus and method for ventricular pacing triggered by detection of early ventricular excitation|
|US6779257||20 Feb 2001||24 Aug 2004||Volcano Therapeutics, Inc.||Method of making a flexible elongate member|
|US6826428||11 Oct 2000||30 Nov 2004||The Board Of Regents Of The University Of Texas System||Gastrointestinal electrical stimulation|
|US6850801||26 Sep 2001||1 Feb 2005||Cvrx, Inc.||Mapping methods for cardiovascular reflex control devices|
|US6859667||7 Nov 2001||22 Feb 2005||Cardiac Pacemakers, Inc.||Multiplexed medical device lead with standard header|
|US6876881||16 Aug 2002||5 Apr 2005||Cardiac Pacemakers, Inc.||Cardiac rhythm management system with respiration synchronous optimization of cardiac performance using atrial cycle length|
|US6894204||2 May 2001||17 May 2005||3M Innovative Properties Company||Tapered stretch removable adhesive articles and methods|
|US6907285||17 Jul 2002||14 Jun 2005||Kenergy, Inc.||Implantable defibrillartor with wireless vascular stent electrodes|
|US6922585||5 Apr 2002||26 Jul 2005||Medtronic, Inc.||Method and apparatus for predicting recurring ventricular arrhythmias|
|US6935344||11 Jan 2000||30 Aug 2005||A-Med Systems, Inc.||Methods and systems for providing right and/or left heart support during cardiac surgery|
|US6937896||26 Feb 2002||30 Aug 2005||Pacesetter, Inc.||Sympathetic nerve stimulator and/or pacemaker|
|US6942622||29 Jul 2002||13 Sep 2005||Pacesetter, Inc.||Method for monitoring autonomic tone|
|US6942686||1 Nov 2002||13 Sep 2005||Coaxia, Inc.||Regulation of cerebral blood flow by temperature change-induced vasodilatation|
|US6985774||26 Sep 2001||10 Jan 2006||Cvrx, Inc.||Stimulus regimens for cardiovascular reflex control|
|US7010337||24 Oct 2002||7 Mar 2006||Furnary Anthony P||Method and apparatus for monitoring blood condition and cardiopulmonary function|
|US7092755||18 Mar 2003||15 Aug 2006||Pacesetter, Inc.||System and method of cardiac pacing during sleep apnea|
|US7123961||7 May 2004||17 Oct 2006||Pacesetter, Inc.||Stimulation of autonomic nerves|
|US7139607||11 Jun 2003||21 Nov 2006||Pacesetter, Inc.||Arrhythmia discrimination|
|US7146226||13 Oct 2004||5 Dec 2006||Paracor Medical, Inc.||Cardiac harness for treating congestive heart failure and for defibrillating and/or pacing/sensing|
|US7155284||16 Jan 2003||26 Dec 2006||Advanced Bionics Corporation||Treatment of hypertension|
|US7158832||26 Sep 2001||2 Jan 2007||Cvrx, Inc.||Electrode designs and methods of use for cardiovascular reflex control devices|
|US7192403||16 Aug 2002||20 Mar 2007||Russell Ted W||Methods, apparatus and articles-of-manufacture for noninvasive measurement and monitoring of peripheral blood flow, perfusion, cardiac output biophysic stress and cardiovascular condition|
|US7225025||30 Sep 2004||29 May 2007||Cardiac Pacemakers, Inc.||Multiplexed medical device lead with standard header|
|US7228179||25 Jul 2003||5 Jun 2007||Advanced Neuromodulation Systems, Inc.||Method and apparatus for providing complex tissue stimulation patterns|
|US7231248||21 Jul 2003||12 Jun 2007||Cardiac Pacemakers, Inc.||Resynchronization method and apparatus based on intrinsic atrial rate|
|US7236821||19 Feb 2002||26 Jun 2007||Cardiac Pacemakers, Inc.||Chronically-implanted device for sensing and therapy|
|US7236861||16 Feb 2005||26 Jun 2007||Lockheed Martin Corporation||Mission planning system with asynchronous request capability|
|US7286878||9 Nov 2001||23 Oct 2007||Medtronic, Inc.||Multiplexed electrode array extension|
|US7321793||13 Jun 2003||22 Jan 2008||Biocontrol Medical Ltd.||Vagal stimulation for atrial fibrillation therapy|
|US7499742||27 Mar 2003||3 Mar 2009||Cvrx, Inc.||Electrode structures and methods for their use in cardiovascular reflex control|
|US7616997||27 Mar 2003||10 Nov 2009||Kieval Robert S||Devices and methods for cardiovascular reflex control via coupled electrodes|
|US7623926||5 Apr 2004||24 Nov 2009||Cvrx, Inc.||Stimulus regimens for cardiovascular reflex control|
|US20010003799||30 Nov 2000||14 Jun 2001||Boveja Birinder Bob||Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator|
|US20010020177||22 Jan 2001||6 Sep 2001||Gruzdowich Gregory J.||Method of blood pressure moderation|
|US20010023367||21 May 2001||20 Sep 2001||King Gary W.||Apparatus and method for expanding a stimulation lead body in situ|
|US20020005982||11 Jan 2001||17 Jan 2002||Rolf Borlinghaus||Arrangement for spectrally sensitive reflected-light and transmitted-light microscopy|
|US20020016548||1 Oct 2001||7 Feb 2002||Medtronic, Inc.||Axis shift analysis of electrocardiogram signal parameters especially applicable for multivector analysis by implantable medical devices, and use of same|
|US20020026228||30 Nov 2000||28 Feb 2002||Patrick Schauerte||Electrode for intravascular stimulation, cardioversion and/or defibrillation|
|US20020058877||25 Oct 2001||16 May 2002||Cardiac Pacemakers, Inc.||Method for measuring baroreflex sensitivity and therapy optimization in heart failure patients|
|US20020068897||4 Dec 2000||6 Jun 2002||Scimed Life Systems, Inc.||Loop structure including inflatable therapeutic device|
|US20020072776||9 Nov 2001||13 Jun 2002||Medtronic, Inc.||Vagal nerve stimulation techniques for treatment of epileptic seizures|
|US20020072782||9 Nov 2001||13 Jun 2002||Medtronic, Inc.||Vagal nerve stimulation techniques for treatment of epileptic seizures|
|US20020103516||20 Sep 2001||1 Aug 2002||Patwardhan Ravish Vinay||Carotid sinus nerve stimulation for epilepsy control|
|US20020107553||26 Oct 2001||8 Aug 2002||Medtronic, Inc.||Method and apparatus for electrically stimulating the nervous system to improve ventricular dysfunction, heart failure, and other cardiac conditions|
|US20020128700||8 Mar 2002||12 Sep 2002||Cross Thomas E.||Lead with adjustable angular and spatial relationships between electrodes|
|US20020143369||26 Oct 2001||3 Oct 2002||Medtronic, Inc.||Method and apparatus to minimize effects of a cardiac insult|
|US20020151051||26 Mar 2002||17 Oct 2002||Sheng Feng Li||Compositions and methods for isolating genes comprising subcellular localization sequences|
|US20020165586||26 Oct 2001||7 Nov 2002||Medtronic, Inc.||Closed-loop neuromodulation for prevention and treatment of cardiac conditions|
|US20020183791||17 Jul 2002||5 Dec 2002||Stephen Denker||Implantable defibrillator with wireless vascular stent electrodes|
|US20030040785||21 Aug 2001||27 Feb 2003||Maschino Steve E.||Circumneural electrode assembly|
|US20030050670||13 Sep 2001||13 Mar 2003||Cardiac Pacemakers, Inc.||Atrial pacing and sensing in cardiac resynchronization therapy|
|US20030060848||26 Sep 2001||27 Mar 2003||Kieval Robert S.||Mapping methods for cardiovascular reflex control devices|
|US20030060857||26 Sep 2001||27 Mar 2003||Perrson Bruce J.||Electrode designs and methods of use for cardiovascular reflex control devices|
|US20030060858||26 Sep 2001||27 Mar 2003||Kieval Robert S.||Stimulus regimens for cardiovascular reflex control|
|US20030078623||22 Oct 2001||24 Apr 2003||Weinberg Lisa P.||Implantable lead and method for stimulating the vagus nerve|
|US20030093130||9 Nov 2001||15 May 2003||Medtronic, Inc.||Multiplexed electrode array extension|
|US20030100924||22 Apr 2002||29 May 2003||Foreman Robert D.||Cardiac neuromodulation and methods of using same|
|US20030120316||20 Dec 2001||26 Jun 2003||Spinelli Julio C.||Cardiac rhythm management system with arrhythmia classification and electrode selection|
|US20030149450||3 Feb 2003||7 Aug 2003||Mayberg Marc R.||Brainstem and cerebellar modulation of cardiovascular response and disease|
|US20030212440||16 Jul 2002||13 Nov 2003||Boveja Birinder R.||Method and system for modulating the vagus nerve (10th cranial nerve) using modulated electrical pulses with an inductively coupled stimulation system|
|US20030229380||31 Oct 2002||11 Dec 2003||Adams John M.||Heart failure therapy device and method|
|US20040010303||27 Mar 2003||15 Jan 2004||Cvrx, Inc.||Electrode structures and methods for their use in cardiovascular reflex control|
|US20040019364||27 Mar 2003||29 Jan 2004||Cvrx, Inc.||Devices and methods for cardiovascular reflex control via coupled electrodes|
|US20040034394||15 Aug 2003||19 Feb 2004||Woods Carla Mann||Implantable generator having current steering means|
|US20040054292||16 Sep 2002||18 Mar 2004||Industrial Technology Research Institute||Non-invasive apparatus system for monitoring autonomic nervous system and uses thereof|
|US20040062852||30 Sep 2002||1 Apr 2004||Medtronic, Inc.||Method for applying a drug coating to a medical device|
|US20040064172||26 Sep 2002||1 Apr 2004||Mcvenes Rick D.||Medical lead with flexible distal guidewire extension|
|US20040102818||26 Nov 2002||27 May 2004||Hakky Said I.||Method and system for controlling blood pressure|
|US20040186523||18 Mar 2003||23 Sep 2004||Florio Joseph J.||System and method of cardiac pacing during sleep apnea|
|US20040193231||20 Nov 2003||30 Sep 2004||Biocontrol Medical Ltd.||Selective nerve fiber stimulation for treating heart conditions|
|US20040199210||11 Jun 2003||7 Oct 2004||Shelchuk Anne M.||Vagal stimulation for improving cardiac function in heart failure or CHF patients|
|US20040210122||1 Nov 2000||21 Oct 2004||Willi Sieburg||Electrical sensing and/or signal application device|
|US20040210271||25 Jul 2003||21 Oct 2004||Campen George Van||Method and apparatus for providing complex tissue stimulation patterns|
|US20040215263||23 Apr 2003||28 Oct 2004||Nathalie Virag||Detection of vasovagal syncope|
|US20040249416||12 Sep 2003||9 Dec 2004||Yun Anthony Joonkyoo||Treatment of conditions through electrical modulation of the autonomic nervous system|
|US20040249417||4 Jun 2003||9 Dec 2004||Terrance Ransbury||Implantable intravascular device for defibrillation and/or pacing|
|US20040254616||5 Apr 2004||16 Dec 2004||Cvrx, Inc.||Stimulus regimens for cardiovascular reflex control|
|US20050010263||29 Jul 2002||13 Jan 2005||Patrick Schauerte||Neurostimulation unit for immobilizing the heart during cardiosurgical operations|
|US20050021092||18 Jun 2004||27 Jan 2005||Yun Anthony Joonkyoo||Treatment of conditions through modulation of the autonomic nervous system|
|US20050065553||10 Jun 2004||24 Mar 2005||Omry Ben Ezra||Applications of vagal stimulation|
|US20050143779||13 Sep 2004||30 Jun 2005||Cardiac Pacemakers, Inc.||Baroreflex modulation based on monitored cardiovascular parameter|
|US20050143785||8 Jun 2004||30 Jun 2005||Imad Libbus||Baroreflex therapy for disordered breathing|
|US20050149126||24 Dec 2003||7 Jul 2005||Imad Libbus||Baroreflex stimulation to treat acute myocardial infarction|
|US20050149127||24 Dec 2003||7 Jul 2005||Imad Libbus||Automatic baroreflex modulation responsive to adverse event|
|US20050149128||24 Dec 2003||7 Jul 2005||Heil Ronald W.Jr.||Barorflex stimulation system to reduce hypertension|
|US20050149129||24 Dec 2003||7 Jul 2005||Imad Libbus||Baropacing and cardiac pacing to control output|
|US20050149130||24 Dec 2003||7 Jul 2005||Imad Libbus||Baroreflex stimulation synchronized to circadian rhythm|
|US20050149131||24 Dec 2003||7 Jul 2005||Imad Libbus||Baroreflex modulation to gradually decrease blood pressure|
|US20050149132||24 Dec 2003||7 Jul 2005||Imad Libbus||Automatic baroreflex modulation based on cardiac activity|
|US20050149133||24 Dec 2003||7 Jul 2005||Imad Libbus||Sensing with compensation for neural stimulator|
|US20050149143||24 Dec 2003||7 Jul 2005||Imad Libbus||Baroreflex stimulator with integrated pressure sensor|
|US20050149155||24 Dec 2003||7 Jul 2005||Avram Scheiner||Stimulation lead for stimulating the baroreceptors in the pulmonary artery|
|US20050149156||24 Dec 2003||7 Jul 2005||Imad Libbus||Lead for stimulating the baroreceptors in the pulmonary artery|
|US20050154418||20 Oct 2004||14 Jul 2005||Kieval Robert S.||Baroreflex activation for pain control, sedation and sleep|
|US20050182468||7 Dec 2004||18 Aug 2005||Angiotech International Ag||Electrical devices and anti-scarring agents|
|US20050197675||18 Feb 2005||8 Sep 2005||Biocontrol Medical Ltd.||Techniques for applying, calibrating, and controlling nerve fiber stimulation|
|US20050251212||20 Jul 2005||10 Nov 2005||Cvrx, Inc.||Stimulus regimens for cardiovascular reflex control|
|US20060004417||27 Jun 2005||5 Jan 2006||Cvrx, Inc.||Baroreflex activation for arrhythmia treatment|
|US20060079945||12 Oct 2004||13 Apr 2006||Cardiac Pacemakers, Inc.||System and method for sustained baroreflex stimulation|
|US20060089678||13 Mar 2003||27 Apr 2006||Alon Shalev||Technique for blood pressure regulation|
|US20060100668||22 Sep 2005||11 May 2006||Biocontrol Medical Ltd.||Selective nerve fiber stimulation|
|US20060111626||29 Dec 2005||25 May 2006||Cvrx, Inc.||Electrode structures having anti-inflammatory properties and methods of use|
|US20060111745||3 Nov 2005||25 May 2006||Foreman Robert D||Cardiac neuromodulation and methods of using same|
|US20060206155||21 Feb 2006||14 Sep 2006||Tamir Ben-David||Parasympathetic pacing therapy during and following a medical procedure, clinical trauma or pathology|
|US20060224222||1 Apr 2005||5 Oct 2006||Kerry Bradley||Apparatus and methods for detecting migration of neurostimulation leads|
|US20070021790||7 Jul 2006||25 Jan 2007||Cvrx, Inc.||Automatic baroreflex modulation responsive to adverse event|
|US20070021792||30 Jun 2006||25 Jan 2007||Cvrx, Inc.||Baroreflex Modulation Based On Monitored Cardiovascular Parameter|
|US20070021794||30 Jun 2006||25 Jan 2007||Cvrx, Inc.||Baroreflex Therapy for Disordered Breathing|
|US20070021796||7 Jul 2006||25 Jan 2007||Cvrx, Inc.||Baroreflex modulation to gradually decrease blood pressure|
|US20070021797||7 Jul 2006||25 Jan 2007||Cvrx, Inc.||Baroreflex stimulation synchronized to circadian rhythm|
|US20070021798||7 Jul 2006||25 Jan 2007||Cvrx, Inc.||Baroreflex stimulation to treat acute myocardial infarction|
|US20070021799||7 Jul 2006||25 Jan 2007||Cvrx, Inc.||Automatic baroreflex modulation based on cardiac activity|
|US20070038255||7 Jul 2006||15 Feb 2007||Cvrx, Inc.||Baroreflex stimulator with integrated pressure sensor|
|US20070038259||7 Jul 2006||15 Feb 2007||Cvrx, Inc.||Method and apparatus for stimulation of baroreceptors in pulmonary artery|
|US20070038260||7 Jul 2006||15 Feb 2007||Cvrx, Inc.||Stimulation lead for stimulating the baroreceptors in the pulmonary artery|
|US20070038261||7 Jul 2006||15 Feb 2007||Cvrx, Inc.||Lead for stimulating the baroreceptors in the pulmonary artery|
|US20070038262||7 Jul 2006||15 Feb 2007||Cvrx, Inc.||Baroreflex stimulation system to reduce hypertension|
|US20070038278||27 May 2005||15 Feb 2007||Cardiac Pacemakers, Inc.||Tubular lead electrodes and methods|
|US20070049989||23 Oct 2006||1 Mar 2007||Cvrx, Inc.||Stimulus regimens for cardiovascular reflex control|
|US20070060972||27 Sep 2006||15 Mar 2007||Cvrx, Inc.||Devices and methods for cardiovascular reflex treatments|
|US20070106340||27 Sep 2006||10 May 2007||Cvrx, Inc.||Electrode structures and methods for their use in cardiovascular reflex control|
|US20070161912||10 Jan 2006||12 Jul 2007||Yunlong Zhang||Assessing autonomic activity using baroreflex analysis|
|US20070167984||7 Jul 2006||19 Jul 2007||Cvrx, Inc.||Method and apparatus for stimulation of baroreceptors|
|US20070179543||24 Jan 2007||2 Aug 2007||Tamir Ben-David||Techniques for prevention of atrial fibrillation|
|US20070185542||28 Dec 2006||9 Aug 2007||Cvrx, Inc.||Baroreflex therapy for disordered breathing|
|US20070185543||13 Apr 2007||9 Aug 2007||Cvrx, Inc.||System and method for sustained baroreflex stimulation|
|US20070191895||21 Nov 2006||16 Aug 2007||Foreman Robert D||Activation of cardiac alpha receptors by spinal cord stimulation produces cardioprotection against ischemia, arrhythmias, and heart failure|
|US20070191904||14 Feb 2006||16 Aug 2007||Imad Libbus||Expandable stimulation electrode with integrated pressure sensor and methods related thereto|
|US20080049376||31 Oct 2007||28 Feb 2008||Greatbatch Ltd.||Non-ferromagnetic tank filters in lead wires of active implantable medical devices to enhance mri compatibility|
|US20080097540||14 Dec 2007||24 Apr 2008||Cvrx, Inc.||Ecg input to implantable pulse generator using carotid sinus leads|
|US20080167694||31 Oct 2007||10 Jul 2008||Cvrx, Inc.||Automatic neural stimulation based on activity|
|US20080167699||31 Oct 2007||10 Jul 2008||Cvrx, Inc.||Method and Apparatus for Providing Complex Tissue Stimulation Parameters|
|US20080171923||31 Oct 2007||17 Jul 2008||Cvrx, Inc.||Assessing autonomic activity using baroreflex analysis|
|US20080172101||31 Oct 2007||17 Jul 2008||Cvrx, Inc.||Non-linear electrode array|
|US20080177339||31 Oct 2007||24 Jul 2008||Cvrx, Inc.||Electrode contact configurations for cuff leads|
|US20080177348||31 Oct 2007||24 Jul 2008||Cvrx, Inc.||Electrode contact configurations for an implantable stimulator|
|US20080177349||31 Oct 2007||24 Jul 2008||Cvrx, Inc.||Apparatus and method for modulating the baroreflex system|
|US20080177350||31 Oct 2007||24 Jul 2008||Cvrx, Inc.||Expandable Stimulation Electrode with Integrated Pressure Sensor and Methods Related Thereto|
|US20080177364||31 Oct 2007||24 Jul 2008||Cvrx, Inc.||Self-locking electrode assembly usable with an implantable medical device|
|US20080177365||31 Oct 2007||24 Jul 2008||Cvrx, Inc.||Method and apparatus for electronically switching electrode configuration|
|US20080177366||31 Oct 2007||24 Jul 2008||Cvrx, Inc.||Cuff electrode arrangement for nerve stimulation and methods of treating disorders|
|US20080215111||31 Oct 2007||4 Sep 2008||Cvrx, Inc.||Devices and Methods for Cardiovascular Reflex Control|
|US20090069738||16 Jul 2008||12 Mar 2009||Cvrx, Inc.||Electrode Structures Having Anti-Inflammatory Properties And Methods Of Use|
|US20090228065||23 Jan 2009||10 Sep 2009||Cvrx, Inc.||Implantable vascular structures and methods for their use|
|US20090234418||9 Apr 2009||17 Sep 2009||Kieval Robert S||Devices and methods for cardiovascular reflex control via coupled electrodes|
|USRE30366||15 Sep 1976||12 Aug 1980||Rasor Associates, Inc.||Organ stimulator|
|WO2001000273A||Title not available|
|WO2003076008A1||13 Mar 2003||18 Sep 2003||Brainsgate Ltd.||Technique for blood pressure regulation|
|1||"Abstracts of the 40th Scientific Sessions", Supplement II to Circulation, vols. XXXV & XXXXVI, Oct. 1967, II-253, 1 sheet.|
|2||Bilgutay et al., "Baropacing a New Concept in the Treatment of Hypertension," from Baroreceptors and Hypertension Proceedings of an International Symposium, Nov. 1965, p. 425-437.|
|3||Bilgutay et al., "Surgical Treatment of Hypertension with Reference to Baropacing," The Amer. Jour. of Cardiology, vol. 17, May 1966, pp. 663-667.|
|4||Bock et al., "Fine Structure of Baroreceptor Terminals in the Carotid Sinus of Guinea Pigs & Mice," Cell & Tissue Research, vol. 170, pp. 95-112 (1976).|
|5||Bolter et al. "Influence of cervical sympathetic nerve stimulation on carotid sinus baroreceptor afferents," Experientia. Nov. 15, 1980;36(11):1301-1302.|
|6||Brattstrom, "Influence of Continuous and Intermittent (R-Wave Triggered) Electrical Stimulation of the Carotid Sinus Nerve on the Static Characteristic of the Circularoty Regulator," Experientia 28:414-416 (1972).|
|7||Braunwald et al., "Carotid Sinus Stimulation in the Treatment of Angina Pectoris and Supraventricular Tachycardia," Calif. Medicine., vol. 112, No. 3, pp. 41-50, Mar. 1970.|
|8||Chiou et al., "Selective Vagal Denervation of the Atria Eliminates Heart Rate Variability and Baroreflex Sensitivity While Preserving Ventricular Innervation," Circulation 1998, 98, pp. 380-368.|
|9||Coleridge et al. "Reflex Effects of Stimulating Baroreceptors in the Pulmonary Artery" J. Physiol. (1963), 166, pp. 197-210.|
|10||Coleridge et al., "Impulse in Slowly Conducting Vagal Fibers from Afferent Endings in the Veins Atria and Arteries of Dogs and Cats," Circ. Res., vol. 33, (Jul. 1973) pp. 87-97.|
|11||Coleridge et al.; Role of the Pulmonary Arterial Baroreceptors in the Effects Produced by Capsaicin in the Dog; J. Physiol. (1964), 170, pp. 272-285.|
|12||Correspondence, The New England of Journal of Medicine, vol. 281, Jul. 3, 1969, No. 2. p. 103.|
|13||Dickinson, CJ, "Fainting Precipitated by Collapse-Firing of Venous Baroreceptors", The Lancet: vol. 342, Oct. 16, 1993, pp. 970-972.|
|14||Ebert et al., "Fentanyl-diazepam anesthesia with or without N20 does not attenuate cardiopulmonary baroreflex-mediated vasoconstrictor responses to controlled hypovolemia in humans," Anesth Analg (1988) vol. 67, No. 6, pp. 548-554.|
|15||Eckberg et al., "Baroreflex Anatomy," In: Monographs of the Physiological Society (43): Human Baroreflexes in Health & Disease, Oxford, UK: Clarendon Press, pp. 19-30, (1992).|
|16||Eckberg et al., "Mechanism of Prolongation of the R-R Interval with Electrical Stimulation of the Carotid Sinus Nerves in Man," Circulation Research, Journal of the American Heart Association, (1972), Dallas, Texas.|
|17||European Search Report for EP01975479, dated Aug. 29, 2005.|
|18||Extended European Search Report for EP09158665, dated Sep. 29, 2009.|
|19||Fan et al., "Graded and dynamic reflex summation of myelinated and unmyelinated rat aortic baroreceptors," Am J Physiol Regul Integr Comp Physiol, Sep. 1999;277(3):R748-756.|
|20||Goldberger et al., "New Technique for Vagal Nerve Stimulation," Journal of Neuroscience Methods, 1999, pp. 109-114.|
|21||Hainsworth, "Cardiovascular Reflexes From Ventricular & Coronary Receptors," Adv. Exp. Med. Biol., 1995, 381:157-74. (61:157-74???).|
|22||Hainsworth, "Reflexes from the Heart," Physiological Reviews, vol. 71, No. 3, (1991).|
|23||Harrison, "Carotid Sinus Stimulation for the Treatment of Angina Pectoris," Official Journal of the Calif. Medical Assoc., vol. 112, No. 3, pp. 78-79, Mar. 1970.|
|24||International Search Report for PCT/US01/30249, dated Jan. 9, 2002.|
|25||International Search Report for PCT/US03/09630, dated Sep. 24, 2003.|
|26||International Search Report for PCT/US03/09764, dated Oct. 28, 2003.|
|27||International Search Report for PCT/US05/11501, dated Aug. 24, 2006.|
|28||International Search Report for PCT/US06/61256, dated Jan. 2, 2008.|
|29||Itoh, "Studies on the Carotid Body & the Carotid Sinus Effects on the Heart by Electrical Stimulation of the Carotid Sinus Wall," Jap. Heart J., vol. 13, No. 2, Mar. 1972, pp. 136-149.|
|30||Kostreva et al., "Hepatic Vein Hapatic Parenchrmal and Inferior Vena Caval Mechanoreceptors with Phrenic Afferents," Am. J. Physiol., vol. 265, 1993, pp. G15-G20.|
|31||Krauhs, "Structure of Rat Aortic Baroreceptors & Their Relationship to Connective Tissue," Journal of Neurocytology, pp. 401-414, 1979.|
|32||Ledsome et al., "Reflex changes in hindlimb and renal vascular resistance in response to distention of the isolated pulmonary arteries of the dog," Circulation Research, Jounal of the American Heart Association, (1977), Dallas, Texas.|
|33||Leung et al., "State of the Art: Sleep Apnea and Cardiovascular Disease," American Journal of Respiratory and Critical Care Medicine, (2001) vol. 164.|
|34||Liguori et al., Arystole and Severe Bradycardia during Epidural Anesthesia in Orthopedic Patients, Anesthesiology: vol. 86(1), Jan. 1997, pp. 250-257.|
|35||Lindblad et al., "Circulatory Effects of Carotid Sinus Stimulation & Changes in Blood Volume Distribution in Hypertensive Man," Acta. Physiol. Scand., 1981, 111:299-306, Mar. 1981.|
|36||Ludbrook et al., "The roles of cardiac receptor and arterial baroreceptor reflexes in control of the circulation during acute change of blood volume in the conscious rabbit," Circulation Research, Journal of the American Heart Association, (1984), Dallas, Texas.|
|37||McLeod et al., "Defining inappropriate practices in prescribing for elderly people: a national consensus panel," Canadian Medical Association, (1997).|
|38||McMAHON et al., "Reflex responses from the main pulmonary artery and bifurcation in anesthetized dogs" Experimental Physiology, 2000 85, 4 pp. 411-419.|
|39||Mifflin et al. "Rapid Resetting of Low Pressure Vagal Receptors in the Superior Vena Cava of the Rat" Circ. Res vol. 51(1982) pp. 241-249.|
|40||Neufeld, "Stimulation of the Carotid Baroreceptors Using a Radio-Frequency Method," Israel J. Med. Sci., vol. 1, No. 4, (Jul. 1965) pp. 630-632.|
|41||Nishi et al. "Afferent Fibres From Pulmonary Arterial Baroreceptors in the Left Cardiac Sympathetic Nerve of the Cat," J. Physiol. 1974 240, pp. 53-66.|
|42||Nusil, White Papers (abstract only), "Drug Delivery Market Summary," published Jun. 25, 2004, retrieved from the internet <<http://www.nusil.com/whitepapers/2004/index.aspx>>.|
|43||Nusil, White Papers (abstract only), "Drug Delivery Market Summary," published Jun. 25, 2004, retrieved from the internet >.|
|44||Office Action for JP 2003-579629, dated Sep. 8, 2008.|
|45||Packer, Calcium Channel blockers in chronic heart failure. The risks of "physiologically rational" therapy, Circulation, Journal of the American Heart Association,(1990), Dallas, Texas.|
|46||Partial European Search Report for EP09158665 dated Jul. 7, 2009.|
|47||Persson et al., "Effect of sino-aortic denervation in comparison to cardiopulmonary deafferentation on long-term blood pressure in conscious dogs," European Journal of Physiology, (1988), pp, 160-166.|
|48||Persson et al., "The influence of cardiopulmonary receptors on long-term blook pressure control and plasma rennin activity in conscious dogs," Acta Physiol Scand (1987).|
|49||Peters et al., "Cardiovascular response to time delays of electrocardiogram-coupled electrical stimulation of carotid sinus nerves in dogs," Journal of the Autonomic Nervous Systems, 25:173-180, 1988.|
|50||Peters et al., "The Principle of Electrical Carotid Sinus Nerve Stimulation: A Nerve Pacemaker System for Angina Pectoris and Hypertension Therapy," Annals of Biomedical Engineering, 8:445-458 (1980).|
|51||Pfeffer "Blood Pressure in Heart Failure: A Love-Hate Relationship," Journal of American Cardiology, (2006).|
|52||Rau et al., "Psychophysiology of Arterial Baroreceptors and the Etiology of Hypertension," Biol. Psychol., vol. 57 (2001) pp. 179-201.|
|53||Reich, "Implantation of a Carotid Sinus Nerve Stimulator," AORN Journal, pp. 53-56, Dec. 1969.|
|54||Richter et al.,"The Course of Inhibition of Sympathetic Activity during Various Patterns of Carotid Sinus Nerve Stimulation", Pflugers Arch. 317:110-123 1970.|
|55||Schauerte et al., "Transvenous Parasympathetic Nerve Stimulation in the Inferior Vena Cava and Atrioventricular Conduction." J. Cardiovasc. Electrophysiol., (Jan. 2000) 11(1):64-69.|
|56||Sedin Gunnar, Responses of the Cardiovascular System to Carotid Sinus Nerve Stimulation, Upsala J Med Sci, 81:1-17 (1976).|
|57||Shahar et al., "Sleep-disordered Breathing and Cardiovascular Disease: Cross-sectional Results of the Sleep Heart Health Study," American Journal of Respiratory and Critical Care Medicine, (2001), vol. 163.|
|58||Silber, "The Treatment of Heart Disease", Heart Disease, 2nd Edition, MacMillan Publishing Co., p. 1642, 1987.|
|59||Silverberg et al., "Treating Obstructive Sleep Apnea Improves Essential Hypertions and Quality of Life," American Family Physician, (2002) vol. 65, No. 2.|
|60||Solti, "Baropacing of the Carotid Sinus Nerve for Treatment of Intractable Hypertension," Zeitschrift Fur Kardiologie, band 64 Heft 4 pp. 368-374, 1975.|
|61||Solti, "The Haemodynamic Basis of Anginal Relief Produced by Stimulation of the Carotid Sinus Nerve," Acta Medica Academiae Scientiarum Hungaricae, vol. 30 (1-2) pp. 61-65 (1973).|
|62||Stefanadis et al., "Non-Invasive Heat-Delivery to Arterial Stented Segments In Vivo: Effect of Heat on Intimal Hyperplasia" J Am Coll Cardiol, 1041-89 Feb. 2000 p. 14A.|
|63||Supplementary European Search Report for EP03716888, dated Nov. 4, 2009.|
|64||Supplementary European Search Report for EP03716913, dated Nov. 4, 2009.|
|65||Supplementary European Search Report for EP05737549, dated Jan. 26, 2010.|
|66||Tarver et al., "Clinical Experience with a Helical Bipolar Stimulating Lead," PACE, vol. 15 Part II (Oct. 1992) pp. 1545-1556.|
|67||Taylor et al., "Non-hypotensive hypovolaemia reduces ascending aortic dimensions in humans," Journal of Physiology, (1995).|
|68||Tsakiris, "Changes in Left Ventricular End Diastolic Volume Pressure Relationship After Acute Cardic Denervation," Abstracts of the 40th Scientific Sessions, Supplement II to Circulation, vols. XXXV & XXXVI, Oct. 1967, II-253, 1 sheet.|
|69||U.S. Appl. No. 10/284,063, filed Oct. 29, 2002.|
|70||U.S. Appl. No. 12/616,057, filed Nov. 10, 2009.|
|71||U.S. Appl. No. 12/719,696, filed Mar. 8, 2010.|
|72||U.S. Appl. No. 12/731,104, filed Mar. 24, 2010.|
|73||U.S. Appln. No. 12/785,287, filed May 21, 2010.|
|74||Warzel et al., "Effects of carotis sinus nerve stimulation at different times in the respiratory and cardiac cycles on variability of heart rate and blood pressure of normotensive and renal hypertensive dogs", Journal of the Autonomic Nervous System, 26:121-127 (1989).|
|75||Warzel et. al., "The Effect of Time of Electrical Stimulation of the Carotid Sinus on the Amount of Reduction in Arterial Pressure", Pflugers Arch., 337:39-44 (1972).|
|76||Yatteau, "Laryngospasm Induced by a Carotid-Sinus-Nerve Stimulator" The New England Journ. of Med., 284 No. 13 pp. 709-710 (1971).|
|Citing Patent||Filing date||Publication date||Applicant||Title|
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|US9480790||20 Nov 2013||1 Nov 2016||The Cleveland Clinic Foundation||Methods and systems for treating acute heart failure by neuromodulation|
|US20080021325 *||12 Jun 2007||24 Jan 2008||Drost Cornelis J||System and method of perivascular pressure and flow measurement|
|International Classification||A61N1/05, A61N1/36, A61N1/00|
|Cooperative Classification||A61N1/36114, A61N1/36135, A61N1/36117, A61N1/36053, A61N1/0551, A61N1/36125, A61N1/36185, A61N1/05, A61N1/3702, A61N1/08, A61B5/02028, A61N1/056, A61N1/3611|
|26 Apr 2010||AS||Assignment|
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